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1.
Comparison of Local and Systemic Ethanol Effects on Extracellular Dopamine Concentration in Rat Nucleus Accumbens by Microdialysis 总被引:4,自引:1,他引:4
Hyeon Joo Yim Timothy Schallert Patrick K. Randall Rueben A. Gonzales 《Alcoholism, clinical and experimental research》1998,22(2):367-374
To determine the site of action of systemic ethanol on dopaminergic function in the nucleus accumbens, we compared the effect of intraperitoneal (ip) and local administration of ethanol on interstitial dopamine concentration using microdialysis in freely moving rats. The ip administration of 1 g/kg of ethanol significantly increased the dialysate dopamine (DA) concentrations (∼40% above basal), compared with saline treatment. The concentration-time profile of DA and ethanol in dialysates was similar after two ethanol injections 4 hr apart. Local perfusion with several ethanol concentrations showed that 510 and 860 mM of ethanol caused a significant concentration-related increase in extracellular DA concentrations in the nucleus accumbens (510 mM, 28% increase; 860 mM, 62% increase). However, lower ethanol concentrations, 170 mM or below, failed to change basal DA concentrations. Stimulation with high potassium (50 mM) in artificial cerebrospinal fluid preceding local ethanol treatment increased dialysate DA concentrations to 523 ± 83% of basal levels, confirming that the DA terminals were responsive to pharmacological manipulation. Basal DA levels in dialysates were ∼70% calcium-dependent when tested at the end of the local perfusion experiments. Stereological examination of the nucleus accumbens revealed probe-induced damage, but did not detect additional damage by local perfusion of ethanol. When ethanol concentrations in the DA sampling area around the probe are taken into account in both systemic and local administration experiments, this study suggests that concentrations of ethanol associated with moderate intoxication do not directly affect the function of DA terminals in the nucleus accumbens. Therefore, the systemic effects of ethanol on nucleus accumbens DAergic function is more likely due to an interaction with sites other than the nucleus accumbens. 相似文献
2.
Sex Differences in Ethanol-induced Dopamine Release in Nucleus Accumbens and in Ethanol Consumption in Rats 总被引:1,自引:0,他引:1
B. A. Blanchard S. Steindorf S. Wang S. D. Glick 《Alcoholism, clinical and experimental research》1993,17(5):968-973
In vivo microdialysis was used to examine changes in nucleus accumbens and striatal dopamine, dihydrophenylacetic acid (DO-PAC), and homovanillic acid (HVA) following acute administration of ethanol (0.0, 0.25, 0.5, 1.0, or 2.0 g/kg) in male and female Long-Evans rats. Following dialysis, rats were trained to bar-press for oral ethanol reinforcement. In nucleus accumbens, females showed significant increases in extracellular dopamine following 0.25 or 0.5 g/ kg ethanol, but did not show significant increases over baseline at the higher doses. Males showed slight increases in dopamine at the lower doses and decreased dopamine at 2.0 g/kg. In striatum, both sexes showed increased dopamine at the lower doses and decreased dopamine at 2.0 g/kg. There were slight increases in nucleus accumbens DOPAC and HVA at some doses in both sexes, but no changes in striatal metabolite levels. In addition to showing increased responsiveness to ethanol-induced mesolimbic dopamine stimulation, females consumed more ethanol than males during behavioral testing. The pattern of both greater ethanol-induced nucleus accumbens dopamine release and greater ethanol consumption in females supports the hypothesis that ethanol reward is mediated, at least in part, by the mesolimbic dopamine system. 相似文献
3.
Kelle M. Franklin Eric A. Engleman Cynthia M. Ingraham Joseph A. McClaren Carrie M. Keith William J. McBride James M. Murphy 《Alcoholism, clinical and experimental research》2009,33(10):1721-1730
Background: The nucleus accumbens (NAc) has been implicated in the neurochemical effects of ethanol (EtOH). Evidence suggests that repeated EtOH exposures and chronic EtOH drinking increase dopamine (DA) neurotransmission in the NAc due, in part, to a reduction in D2 autoreceptor function. The objectives of the current study were to evaluate the effects of a single EtOH pretreatment and repeated EtOH pretreatments on DA neurotransmission and D2 autoreceptor function in the NAc of Wistar rats. Methods: Experiment 1 examined D2 receptor function after a single intraperitoneal (i.p.) injection or repeated i.p. injections of 0.0, 0.5, 1.0, or 2.0 g/kg EtOH to female Wistar rats. Single EtOH pretreatment groups received 1 daily i.p. injection of 0.9% NaCl (saline) for 4 days, followed by 1 day of saline or EtOH administration; repeated EtOH pretreatment groups received 5 days of saline or EtOH injections. Reverse microdialysis experiments were conducted to determine the effects of local perfusion with the D2‐like receptor antagonist (‐)sulpiride (SUL; 100 uM), on extracellular DA levels in the NAc. Experiment 2 evaluated if pretreatment with a single, moderate (1.0 g/kg) dose of EtOH would alter levels and clearance of extracellular DA in the NAc, as measured by no‐net‐flux (NNF) microdialysis. Subjects were divided into the EtOH‐naïve and the single EtOH pretreated groups from Experiment 1. Results: Experiment 1: Changes in extracellular DA levels induced with SUL perfusion were altered by the EtOH dose (p < 0.001), but not the number of EtOH pretreatments (p > 0.05). Post‐hoc analyses indicated that groups pretreated with single or repeated 1.0 g/kg EtOH showed significantly attenuated DA response to SUL, compared with all other groups (p < 0.001). Experiment 2: Multiple linear regression analyses yielded significantly (p < 0.05) higher extracellular DA concentrations in the NAc of rats receiving EtOH pretreatment, compared with their EtOH‐naïve counterparts (3.96 ± 0.42 nM and 3.25 ± 0.23 nM, respectively). Extraction fractions were not significantly different between the 2 groups. Conclusions: The present results indicate that a single EtOH pretreatment at a moderate dose can increase DA neurotransmission in the NAc due, in part, to reduced D2 autoreceptor function. 相似文献
4.
B. A. Blanchard S. Steindorf S. Wang R. LeFevre R. F. Mankes S. D. Glick 《Alcoholism, clinical and experimental research》1993,17(5):974-981
Using in vivo microdialysis, ethanol-induced dopamine release in nucleus accumbens and striatum was examined in adult male and female Long-Evans rats exposed prenatally to ethanol and in controls. Following dialysis, ethanol intake was measured in an operant paradigm. Control rats showed increased dopamine release in nucleus accumbens and striatum in response to 0.5 g/kg ethanol, but not to 1.0 g/kg. Fetal ethanol-exposed rats showed no dopamine response at 0.5 g/kg. At 1.0 g/kg, fetal ethanol-exposed males showed increased dopamine release in both structures. Prenatally exposed females showed no change in accumbens, and decreased release in striatum. Fetal ethanol exposure did not significantly influence ethanol intake. The findings suggest that prenatal ethanol exposure influences subsequent neurochemical responses to ethanol; however, how these neurochemical measures are related to ethanol intake could not be determined in the present study. Data are discussed in terms of sex-specific shifts in the dose-response function for ethanol-induced dopamine release resulting from prenatal ethanol exposure. 相似文献
5.
Ethanol Enhances the Release of Dopamine and Serotonin in the Nucleus Accumbens of HAD and LAD Lines of Rats 总被引:4,自引:0,他引:4
K. Yoshimoto W. J. McBride L. Lumeng T.-K. Li 《Alcoholism, clinical and experimental research》1992,16(4):781-785
The effects of intraperitoneal administration of ethanol, 0.5, 1.0, and 2.0 g/kg body weight, on the extracellular concentrations of dopamine (DA), serotonin (5-HT), and their major metabolites were studied in the nucleus accumbens (ACC) of alcohol-naive, selectively bred high-alcohol-drinking (HAD) and low-alcohol-drinking (LAD) lines of rats using the technique of microdialysis. In both lines, the extracellular levels of DA were increased following the injection of 1.0 and 2.0 g of ethanol/kg body weight while only the 2.0-g/kg dose elevated the concentration of 5-HT. None of the ethanol doses altered the extracellular levels of the major metabolites of DA and 5-HT. Dose-response curves for DA and 5-HT release indicated no marked difference in the sensitivity to ethanol between the lines. Local perfusion with 60 mM K+ through the microdialysis probe markedly enhanced the release of DA and 5-HT in the ACC of both lines; there was a small difference between the lines in the amounts of DA, but not 5-HT, released by K(+)-stimulation. Overall, the results indicate that (1) the ACC DA system is more sensitive than the ACC 5-HT system to intraperitoneal ethanol administration in both lines and (2) there is no evidence for a relationship between alcohol preference and sensitivity of the ACC DA and 5-HT systems to acute intraperitoneal ethanol administration. 相似文献
6.
Elaina C. Howard Christina J. Schier Jeremy S. Wetzel Rueben A. Gonzales 《Alcoholism, clinical and experimental research》2009,33(8):1355-1365
Background: Ethanol self-administration has been shown to increase dopamine in the nucleus accumbens; however, dopamine levels in the accumbal subregions (core, shell, and core–shell border) have not yet been measured separately in this paradigm. This study was designed to determine if dopamine responses during operant ethanol self-administration are similar in the core, core–shell border, and shell, particularly during transfer from the home cage to the operant chamber and during consumption of the drinking solution.
Methods: Six groups of male Long–Evans rats were trained to lever-press for either 10% sucrose (10S) or 10% sucrose + 10% ethanol (10S10E) (with a guide cannula above the core, core–shell border, or shell of the accumbens). On experiment day, 5-minute microdialysis samples were collected from the core, core–shell border, or shell before, during, and after drinking. Dopamine and ethanol concentrations were analyzed in these samples.
Results: A significant increase in dopamine occurred during transfer of the rats from the home cage into the operant chamber in all 6 groups, with those trained to drink 10S10E exhibiting a significantly higher increase than those trained to drink 10S in the core and shell. No significant increases were observed during drinking of either solution in the core or shell. A significant increase in dopamine was observed during consumption of ethanol in the core–shell border.
Conclusions: We conclude that dopamine responses to operant ethanol self-administration are subregion specific. After operant training, accumbal dopamine responses in the core and shell occur when cues that predict ethanol availability are presented and not when the reinforcer is consumed. However, core–shell border dopamine responses occur at the time of the cue and consumption of the reinforcer. 相似文献
Methods: Six groups of male Long–Evans rats were trained to lever-press for either 10% sucrose (10S) or 10% sucrose + 10% ethanol (10S10E) (with a guide cannula above the core, core–shell border, or shell of the accumbens). On experiment day, 5-minute microdialysis samples were collected from the core, core–shell border, or shell before, during, and after drinking. Dopamine and ethanol concentrations were analyzed in these samples.
Results: A significant increase in dopamine occurred during transfer of the rats from the home cage into the operant chamber in all 6 groups, with those trained to drink 10S10E exhibiting a significantly higher increase than those trained to drink 10S in the core and shell. No significant increases were observed during drinking of either solution in the core or shell. A significant increase in dopamine was observed during consumption of ethanol in the core–shell border.
Conclusions: We conclude that dopamine responses to operant ethanol self-administration are subregion specific. After operant training, accumbal dopamine responses in the core and shell occur when cues that predict ethanol availability are presented and not when the reinforcer is consumed. However, core–shell border dopamine responses occur at the time of the cue and consumption of the reinforcer. 相似文献
7.
Alcohol Self-Administration: Further Examination of the Role of Dopamine Receptors in the Nucleus Accumbens 总被引:8,自引:0,他引:8
Clyde W. Hodge Herman H. Samson Ann M. Chappelle 《Alcoholism, clinical and experimental research》1997,21(6):1083-1091
One of the functions of the mesolimbic dopamine (DA) system is to regulate the process of reinforcement, a process that is thought to influence drug self-administration. This study tested the effects of centrally administered DA receptor ligands on ethanol self-administration behavior. Long-Evans rats were trained to lever press on a fixed-ratio 4 schedule of ethanol (10% v/v) reinforcement. DA agonists and antagonists were then bilaterally microinjected (0.5 μ/side) into the nucleus accumbens (N Acc) 10-min before sessions to test for effects on the onset, maintenance, and termination of ethanol self-administration. Infusions of the D1-like agonist SKF 38393 (0.03 to 3.0 μg) produced no effect on ethanol self-administration. The D1-like antagonist SCH 23390 (0.5 to 2.0 μg) reduced total responding by decreasing the time course of self-administration without altering response rate. The D2-like agonist quinpirole produced a biphasic effect on self-administration. Quinpirole (1.0 μg) increased total responses and response rate, whereas higher doses (4.0 to 10.0 μg) decreased total responding as a result of early termination. The D2-like antagonist raclopride (0.1 to 1.0 μg) reduced total responding by decreasing time course and response rate. Co-administration of either SKF 38393 or SCH 23390 with quinpirole prevented the behavioral effects observed with the low doses of quinpirole. Thus, in the N ACC either increased activation of D1-like receptors or their blockade can affect the expression of the behavioral effects of the D2-like agonist. This suggests that some intermediate level of D1 activation is required to observe the D2 effect. The decreases in total responding produced by raclopride were enhanced by co-administration of SKF 38393, but not altered by SCH 23390, thus suggesting that D1-like and D2-like receptors in the N Acc interact in the regulation of ethanol self-administration in a manner similar to their interactive regulation of other behaviors. 相似文献
8.
Helga Höifödt Lidö Rosita Stomberg Anne Fagerberg Mia Ericson Bo Söderpalm 《Alcoholism, clinical and experimental research》2009,33(7):1151-1157
Background: The mesolimbic dopamine (DA) projection from the ventral tegmental area to nucleus accumbens (nAc), a central part of the reward system, is activated by ethanol (EtOH) and other drugs of abuse. We have previously demonstrated that the glycine receptor in the nAc and its amino acid agonists may be implicated in the DA activation and reinforcing properties of EtOH. We have also reported that the glycine transporter 1 inhibitor, Org 25935, produces a robust and dose-dependent decrease in EtOH consumption in Wistar rats. The present study explores the interaction between EtOH and Org 25935 with respect to DA levels in the rat nAc.
Methods: The effects of Org 25935 (6 mg/kg, i.p.) and/or EtOH (2.5 g/kg, i.p.) on accumbal DA levels were examined by means of in vivo microdialysis (coupled to HPLC-ED) in freely moving male Wistar rats. The effect of Org 25935 on accumbal glycine output was also investigated.
Results: Systemic Org 25935 increased DA output in a subpopulation of rats (52% in Experiment 1 and 38% in Experiment 2 ). In Experiment 2 , EtOH produced a significant increase in DA levels in vehicles (35%) and in Org 25935 nonresponders (19%), whereas EtOH did not further increase the DA level in rats responding to Org 25935 (2%). The same dose of Org 25935 increased glycine levels by 87% in nAc.
Conclusions: This study demonstrates that Org 25935, probably via increased glycine levels, (i) counteracts EtOH-induced increases of accumbal DA levels and (ii) increases basal DA levels in a subpopulation of rats. The results are in line with previous findings and it is suggested that the effects observed involve interference with accumbal GlyRs and are related to the alcohol consumption modulating effect of Org 25935. 相似文献
Methods: The effects of Org 25935 (6 mg/kg, i.p.) and/or EtOH (2.5 g/kg, i.p.) on accumbal DA levels were examined by means of in vivo microdialysis (coupled to HPLC-ED) in freely moving male Wistar rats. The effect of Org 25935 on accumbal glycine output was also investigated.
Results: Systemic Org 25935 increased DA output in a subpopulation of rats (52% in Experiment 1 and 38% in Experiment 2 ). In Experiment 2 , EtOH produced a significant increase in DA levels in vehicles (35%) and in Org 25935 nonresponders (19%), whereas EtOH did not further increase the DA level in rats responding to Org 25935 (2%). The same dose of Org 25935 increased glycine levels by 87% in nAc.
Conclusions: This study demonstrates that Org 25935, probably via increased glycine levels, (i) counteracts EtOH-induced increases of accumbal DA levels and (ii) increases basal DA levels in a subpopulation of rats. The results are in line with previous findings and it is suggested that the effects observed involve interference with accumbal GlyRs and are related to the alcohol consumption modulating effect of Org 25935. 相似文献
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Association between Low Contents of Dopamine and Serotonin in the Nucleus Accumbens and High Alcohol Preference 总被引:3,自引:0,他引:3
W. J. McBride B. Bodart L. Lumeng T.-K. Li 《Alcoholism, clinical and experimental research》1995,19(6):1420-1422
The contents of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), serotonin (5-HT), and 5-hydroxy-indoleacetic acid (5-HIAA) were determined in the nucleus accumbens (ACB), frontal cortex (FR), anterior striatum (AST), and hippocampus (HIP) of adult male rats from the F2 generation of P×NP intercrosses. Rats were tested for their alcohol preference and were divided into two groups, depending on their alcohol intake. Rats in the high drinking group ( n = 11) had ethanol intakes >5 g/kg/day, whereas the low drinking group ( n = 15) had values < 1 g/kg/day. The content of DA in the ACB was lower ( p < 0.001) in the high alcohol drinking group (46 ± 2 pmol/mg tissue) than in the low intake rats (61 ± 3 pmol/mg tissue). However, the contents of DOPAC and HVA in the ACB were similar for both groups. There were no differences between the two groups in the contents of DA in the FR or AST. The content of 5-HT in the ACB was lower (p < 0.05) in high alcohol drinking rats (6.3 ± 0.3 pmol/mg tissue) than in the low intake group (7.0 ± 0.2 pmol/mg tissue). The content of 5-HIAA in the ACB of the high intake rats was also lower than the level for the low drinking rats. There were no differences in the contents of 5-HT or 5-HIAA in the FR, HIP, and AST between the two groups. The results confirm a phenotypic association between abnormal DA and 5-HT systems projecting to the ACB and high alcohol drinking behavior in the P line of rats. 相似文献
11.
Ethanol Inhibits Single-Unit Responses in the Nucleus Accumbens Evoked by Stimulation of the Basolateral Nucleus of the Amygdala 总被引:1,自引:0,他引:1
José R. Criado Rong-Sheng Lee Greta I. Berg Steven J. Henriksen 《Alcoholism, clinical and experimental research》1997,21(2):368-374
We studied the actions of intoxicating doses of ethanol on excitatory inputs from the basolateral nucleus of the amygdala, a major afferent system projecting to the nucleus accumbens (NAcc). In view of the hypothesized role of opioid receptors on the effects of ethanol on NAcc physiology, we also explored whether naloxone modulates ethanol-induced suppression of NAcc excitability in halothane anesthetized and freely moving unanesthetized rats. Intraperitoneal administration of ethanol (1.2–1.4 g/kg) markedly suppressed a subgroup of amygdala-activated NAcc neurons. The ethanol-induced reduction in amygdala-activated NAcc neurons was not reversed by naloxone (5.0 mg/kg, intraperitoneally). Moreover, naloxone had no effect on the supressive effects of ethanol on NAcc spontaneous activity in either halothane-anesthetized or unanesthetized freely moving preparations. These findings suggest that opiate mechanisms either are not participating or are not solely responsible for the inhibitory effects of acute intoxicating doses of ethanol on NAcc physiology. 相似文献
12.
Donita L. Robinson Elaina C. Howard Scott McConnell Rueben A. Gonzales R. Mark Wightman 《Alcoholism, clinical and experimental research》2009,33(7):1187-1196
Background: Dopamine concentrations in the nucleus accumbens fluctuate on phasic (subsecond) and tonic (over minutes) timescales in awake rats. Acute ethanol increases tonic concentrations of dopamine, but its effect on subsecond dopamine transients has not been fully explored.
Methods: We measured tonic and phasic dopamine fluctuations in the nucleus accumbens of rats in response to ethanol (within-subject cumulative dosing, 0.125 to 2 g/kg, i.v.).
Results: Microdialysis samples yielded significant tonic increases in dopamine concentrations at 1 to 2 g/kg ethanol in each rat, while repeated saline infusions had no effect. When monitored with fast scan cyclic voltammetry, ethanol increased the frequency of dopamine transients in 6 of 16 recording sites, in contrast to the uniform effect of ethanol as measured with microdialysis. In the remaining 10 recording sites that were unresponsive to ethanol, dopamine transients either decreased in frequency or were unaffected by cumulative ethanol infusions, patterns also observed during repeated saline infusions. The responsiveness of particular recording sites to ethanol was not correlated with either core versus shell placement of the electrodes or the basal rate of dopamine transients. Importantly, the phasic response pattern to a single dose of ethanol at a particular site was qualitatively reproduced when a second dose of ethanol was administered, suggesting that the variable between-site effects reflected specific pharmacology at that recording site.
Conclusions: These data demonstrate that the relatively uniform dopamine concentrations obtained with microdialysis can mask a dramatic heterogeneity of phasic dopamine release within the accumbens. 相似文献
Methods: We measured tonic and phasic dopamine fluctuations in the nucleus accumbens of rats in response to ethanol (within-subject cumulative dosing, 0.125 to 2 g/kg, i.v.).
Results: Microdialysis samples yielded significant tonic increases in dopamine concentrations at 1 to 2 g/kg ethanol in each rat, while repeated saline infusions had no effect. When monitored with fast scan cyclic voltammetry, ethanol increased the frequency of dopamine transients in 6 of 16 recording sites, in contrast to the uniform effect of ethanol as measured with microdialysis. In the remaining 10 recording sites that were unresponsive to ethanol, dopamine transients either decreased in frequency or were unaffected by cumulative ethanol infusions, patterns also observed during repeated saline infusions. The responsiveness of particular recording sites to ethanol was not correlated with either core versus shell placement of the electrodes or the basal rate of dopamine transients. Importantly, the phasic response pattern to a single dose of ethanol at a particular site was qualitatively reproduced when a second dose of ethanol was administered, suggesting that the variable between-site effects reflected specific pharmacology at that recording site.
Conclusions: These data demonstrate that the relatively uniform dopamine concentrations obtained with microdialysis can mask a dramatic heterogeneity of phasic dopamine release within the accumbens. 相似文献
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Zheng-Ming Ding Zachary A. Rodd Eric A. Engleman William J. McBride 《Alcoholism, clinical and experimental research》2009,33(9):1571-1581
Background: Previous studies indicated that chronic alcohol drinking increased the sensitivity of the posterior ventral tegmental area (p-VTA) to the reinforcing effects of ethanol. The current study tested the hypothesis that local exposure of the p-VTA to ethanol would increase the sensitivity of dopamine (DA) neurons to the stimulating effects of ethanol.
Methods: Experiment 1 examined the stimulating effects of ethanol in the p-VTA after a 7-day ethanol pretreatment in the p-VTA. Adult female Wistar rats were pretreated with microinjections of 200 mg% ethanol or artificial cerebrospinal fluid (aCSF) into the p-VTA once a day for 7 days. On the eighth day, rats received a challenge injection of ethanol (100, 200, or 300 mg%) or aCSF into the p-VTA, and extracellular DA levels were measured in the nucleus accumbens (NAc) shell with microdialysis. Experiment 2 examined the stimulating effects of ethanol (200 mg%) after a 3- or 5-day ethanol (200 mg%) pretreatment in the p-VTA. Experiment 3 examined the stimulating effects of ethanol (200 mg%) 7 days after the last of the 7-day ethanol (200 mg%) pretreatments in the p-VTA.
Results: Experiment 1: in both aCSF- and ethanol-pretreated rats, the challenge microinjection of ethanol dose-dependently increased DA release in the NAc shell, with significantly greater increases in ethanol-pretreated groups. Experiment 2: the 5-day, but not 3-day, ethanol pretreatment protocol increased the response of p-VTA dopamine neurons to the ethanol challenge. Experiment 3: the increased stimulating effects of ethanol were still evident after 7 days.
Conclusions: The results indicate that repeated local ethanol exposure of the p-VTA produced neuroadaptations in DA neurons projecting to the NAc shell, resulting in a persistent increase in the sensitivity of these neurons to the stimulating effects of ethanol. 相似文献
Methods: Experiment 1 examined the stimulating effects of ethanol in the p-VTA after a 7-day ethanol pretreatment in the p-VTA. Adult female Wistar rats were pretreated with microinjections of 200 mg% ethanol or artificial cerebrospinal fluid (aCSF) into the p-VTA once a day for 7 days. On the eighth day, rats received a challenge injection of ethanol (100, 200, or 300 mg%) or aCSF into the p-VTA, and extracellular DA levels were measured in the nucleus accumbens (NAc) shell with microdialysis. Experiment 2 examined the stimulating effects of ethanol (200 mg%) after a 3- or 5-day ethanol (200 mg%) pretreatment in the p-VTA. Experiment 3 examined the stimulating effects of ethanol (200 mg%) 7 days after the last of the 7-day ethanol (200 mg%) pretreatments in the p-VTA.
Results: Experiment 1: in both aCSF- and ethanol-pretreated rats, the challenge microinjection of ethanol dose-dependently increased DA release in the NAc shell, with significantly greater increases in ethanol-pretreated groups. Experiment 2: the 5-day, but not 3-day, ethanol pretreatment protocol increased the response of p-VTA dopamine neurons to the ethanol challenge. Experiment 3: the increased stimulating effects of ethanol were still evident after 7 days.
Conclusions: The results indicate that repeated local ethanol exposure of the p-VTA produced neuroadaptations in DA neurons projecting to the NAc shell, resulting in a persistent increase in the sensitivity of these neurons to the stimulating effects of ethanol. 相似文献
15.
Eric A. Engleman Zheng-Ming Ding Scott M. Oster Jamie E. Toalston Richard L. Bell James M. Murphy William J. McBride Zachary A. Rodd 《Alcoholism, clinical and experimental research》2009,33(12):2162-2171
Background: A previous study indicated that selectively bred alcohol-preferring (P) rats self-administered ethanol (EtOH) directly into the posterior ventral tegmental area at lower concentrations than Wistar rats. The present study was undertaken to determine involvement of the nucleus accumbens (Acb) with EtOH reinforcement, and a relationship between genetic selection for high alcohol preference and sensitivity of the Acb to the reinforcing effects of EtOH.
Methods: Adult P and Wistar rats were assigned to groups that self-infused 0 to 300 mg% EtOH into the Acb shell (AcbSh) or Acb Core (AcbC). Rats were placed into 2-lever (active and inactive) operant chambers and given EtOH for the first 4 sessions (acquisition), artificial cerebrospinal fluid (aCSF) for sessions 5 and 6 (extinction), and EtOH again in session 7 (reinstatement). Responding on the active lever produced a 100-nl injection of the infusate.
Results: Alcohol-preferring rats self-infused 75 to 300 mg% EtOH, whereas Wistar rats reliably self-infused 100 and 300 mg% EtOH into the AcbSh. Both P and Wistar rats reduced responding on the active lever when aCSF was substituted for EtOH, and reinstated responding in session 7 when EtOH was restored. EtOH was not self-infused into the AcbC by P or Wistar rats.
Conclusions: The present results indicate that the AcbSh, but not AcbC, is a neuroanatomical structure that mediates the reinforcing actions of EtOH. The data also suggest that, compared to Wistar rats, the AcbSh of P rats is more sensitive to the reinforcing effects of EtOH. 相似文献
Methods: Adult P and Wistar rats were assigned to groups that self-infused 0 to 300 mg% EtOH into the Acb shell (AcbSh) or Acb Core (AcbC). Rats were placed into 2-lever (active and inactive) operant chambers and given EtOH for the first 4 sessions (acquisition), artificial cerebrospinal fluid (aCSF) for sessions 5 and 6 (extinction), and EtOH again in session 7 (reinstatement). Responding on the active lever produced a 100-nl injection of the infusate.
Results: Alcohol-preferring rats self-infused 75 to 300 mg% EtOH, whereas Wistar rats reliably self-infused 100 and 300 mg% EtOH into the AcbSh. Both P and Wistar rats reduced responding on the active lever when aCSF was substituted for EtOH, and reinstated responding in session 7 when EtOH was restored. EtOH was not self-infused into the AcbC by P or Wistar rats.
Conclusions: The present results indicate that the AcbSh, but not AcbC, is a neuroanatomical structure that mediates the reinforcing actions of EtOH. The data also suggest that, compared to Wistar rats, the AcbSh of P rats is more sensitive to the reinforcing effects of EtOH. 相似文献
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José R. Criado Rong-Sheng Lee Greta I. Berg Steven J. Henriksen 《Alcoholism, clinical and experimental research》1995,19(1):164-169
The nucleus accumbens septi (NAcc) is considered an important component of the final common pathway involved in the reinforcing properties of ethanol. We studied the effects of intraperitoneal administration of ethanol on spontaneous, glutamate-activated, and fimbria-activated NAcc neurons in acute anesthetized and freely moving unanesthetized rats. Ethanol significantly reduced the firing rate of spontaneous and glutamate-activated NAcc neurons in both electrophysiological preparations. Stimulation of the ipsilateral fimbria evoked single-unit activity in NAcc neurons with two characteristic latencies (early, 7.21 ± 0.74 msec; late, 18.24 ± 0.66 msec). Intoxicating doses of ethanol inhibited the recruitment of late, but not of early, fimbria-activated NAcc neurons. These data demonstrate electrophysiological evidence for the existence of neurons in the core region of the NAcc that are sensitive and insensitive to acute systemic ethanol administration. 相似文献
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Cristine L. Czachowski Ann M. Chappell Herman H. Samson 《Alcoholism, clinical and experimental research》2001,25(10):1431-1440
BACKGROUND: Nucleus accumbens dopamine has been shown to play a role in the processing of behaviorally relevant stimuli and to mediate ethanol-reinforced responding. Previous research that used a fixed-ratio schedule of responding maintained by the presentation of small dippers (0.1 ml) of ethanol demonstrated that the dopamine D2 antagonist, raclopride, decreased total responding for ethanol by both delaying the onset of responding and causing the early termination of lever-press behavior. Because these studies required animals to continuously respond to obtain access to small amounts of ethanol over a period of self-administration, this procedure assessed a combination of appetitive (seeking) and consummatory (drinking) behavior. The paradigm used in the present study separated the appetitive or seeking response from the consummatory response to assess the effects of raclopride on both types of ethanol-related behaviors. METHODS: Male Long-Evans rats were trained to emit a fixed number of lever-press responses that resulted in access to a drinking tube that contained 10% ethanol for 20 min, once each day. We measured the effects of microinjections of raclopride (1.0, 3.0, and 10.0 microg/subject) into the nucleus accumbens, before the sessions, on appetitive and consummatory responding. RESULTS: Raclopride delayed the onset of ethanol-seeking (appetitive responding) at all doses and decreased the number of responses made at the low and high doses. The rate of responding, however, was unaffected. Raclopride had no effect on the latency to begin consuming ethanol or on any of the characteristics of the initial bout of ethanol intake at all doses tested. Total ethanol intake was decreased, after an initially "normal" pattern of self-administration, following only the highest dose of raclopride. Mean ethanol intake (g/kg) was 0.54 (+/-0.03) after no injection, 0.51 (+/-0.04) after sham treatment, and 0.38 (+/-0.05) after 10 microg of raclopride. CONCLUSIONS: The procedural separation of the seeking and intake responses used in this experiment allowed us to assess the effects of dopamine receptor antagonism in the nucleus accumbens on these two different behaviors. Overall, appetitive responding that preceded the delivery of an ethanol solution was more sensitive to raclopride treatment than was consummatory responding. These findings are consistent with a stimulus-processing function of the mesolimbic dopamine system. 相似文献
20.
In Vivo Study of Salsolinol Produced by a High Concentration of Acetaldehyde in the Striatum and Nucleus Accumbens of Free-Moving Rats 总被引:1,自引:0,他引:1
Mostofa Jamal Kiyoshi Ameno Setsuko Ameno Naoko Okada Iwao Ijiri 《Alcoholism, clinical and experimental research》2003,27(S1):79S-84S
Background: Salsolinol, a neuropharmacologically active compound, is formed by the condensation of acetaldehyde (AcH) with dopamine (DA) in the brain. The aim of our study was to examine the effect of a high concentration of AcH on salsolinol formation and to compare the release of DA, serotonin (5-HT), and salsolinol in the striatum and nucleus accumbens (NAc) in free-moving rats.
Methods: After the insertion of a microdialysis probe, male Wistar rats (250–300 g) were treated with cyanamide (CY, a potent aldehyde dehydrogenase inhibitor) + ethanol (EtOH), CY + 4-methylpyrazole (4-MP, a strong alcohol dehydrogenase inhibitor) + EtOH, 4-MP + EtOH, CY, and 4-MP. Simultaneous quantitation of DA, 5-HT, and salsolinol in dialysates was performed by using in vivo microdialysis coupled with high-performance liquid chromatography with an electrochemical detector and blood EtOH and AcH by using a head-space gas chromatographic method.
Results: Salsolinol was detected only in the CY + EtOH groups in both the striatum and NAc, and we also detected a high AcH concentration in the blood in those groups. A correlation was found between the dialysate levels of salsolinol and blood concentrations of AcH. The striatal levels of DA and 5-HT were approximately two times higher, whereas salsolinol levels were approximately three times higher compared with the usual level in the NAc. No significant difference of DA and 5-HT levels in the dialysates was observed in either the control or the other study groups.
Conclusion: Our observation suggested that the brain salsolinol formation may depend on the concentrations of DA and AcH in freely moving rats, and there is no effect of a high concentration of AcH on DA and 5-HT levels in the striatum and NAc. 相似文献
Methods: After the insertion of a microdialysis probe, male Wistar rats (250–300 g) were treated with cyanamide (CY, a potent aldehyde dehydrogenase inhibitor) + ethanol (EtOH), CY + 4-methylpyrazole (4-MP, a strong alcohol dehydrogenase inhibitor) + EtOH, 4-MP + EtOH, CY, and 4-MP. Simultaneous quantitation of DA, 5-HT, and salsolinol in dialysates was performed by using in vivo microdialysis coupled with high-performance liquid chromatography with an electrochemical detector and blood EtOH and AcH by using a head-space gas chromatographic method.
Results: Salsolinol was detected only in the CY + EtOH groups in both the striatum and NAc, and we also detected a high AcH concentration in the blood in those groups. A correlation was found between the dialysate levels of salsolinol and blood concentrations of AcH. The striatal levels of DA and 5-HT were approximately two times higher, whereas salsolinol levels were approximately three times higher compared with the usual level in the NAc. No significant difference of DA and 5-HT levels in the dialysates was observed in either the control or the other study groups.
Conclusion: Our observation suggested that the brain salsolinol formation may depend on the concentrations of DA and AcH in freely moving rats, and there is no effect of a high concentration of AcH on DA and 5-HT levels in the striatum and NAc. 相似文献