共查询到20条相似文献,搜索用时 0 毫秒
1.
The mu- and delta-opioid receptors located at the terminal level in nucleus accumbens are involved in the opiate modulation of dopamine release in this brain area. However, recent studies suggest that the effects of opioid drugs on the core subregion of nucleus accumbens may completely differ from those observed in the shell. We used in vivo microdialysis to simultaneously apply selective mu- and delta-opioid receptor agonists and to measure extracellular levels of dopamine in three subregions of the accumbens, namely shell, core, and the transition zone between them. The regional analysis of these subregions of the accumbens demonstrated that basal levels of dopamine and its metabolites were higher in the core, and decreased from this subregion to the shell. Retrodialysis application to the core of both the selective mu-receptor agonist ([D-Ala(2), N-Me-Phe(4), Gly(5)-ol]-enkephalin (DAMGO) (1 micromol/L)) and of the selective delta-opioid receptor agonist ([D-Pen(2), D-Pen(5)]-enkephalin (DPDPE) (50 nmol/L)) increased the dialysate levels of dopamine. However, the application of these drugs to the shell significantly reduced the dopamine levels in this subregion. Local application of the same doses of these drugs in the transition zone between the shell and the core did not significantly affect the dopamine levels in dialysates. These results suggest that the opioid circuits modulating dopaminergic activity in the shell could differ from those in the core of the nucleus accumbens. 相似文献
2.
Increased conditioned fear response and altered balance of dopamine in the shell and core of the nucleus accumbens during amphetamine withdrawal 总被引:2,自引:0,他引:2
It has been suggested that neuroadaptations within the nucleus accumbens (NAC) dopaminergic (DA) projection contribute to the negative affect associated with psychostimulant withdrawal. The present study assessed the effects of amphetamine (AMPH) withdrawal on behavioral and NAC DA responses to conditioned fear stress. Animals injected with escalating-dose AMPH (1-5mg/kg, three injections/day, 6 days) or saline (SAL) acquired a tone-shock association on withdrawal day 3 and were tested for extinction of conditioned freezing to the tone on withdrawal day 4. Extracellular levels of NAC shell and core DA were monitored using in vivo microdialysis on both days. AMPH-withdrawn animals exhibited more conditioned freezing than SAL animals during both acquisition and extinction. During acquisition, DA increased more in the shell than the core of the NAC in both AMPH and SAL groups. During extinction to the tone, shell DA increased in SAL- but not AMPH-treated animals, whereas core DA activity was greater in AMPH than SAL animals. These data demonstrate that AMPH withdrawal alters the balance between shell and core DA transmission while increasing the behavioral expression of conditioned fear. Such drug-induced neuroadaptations in the NAC stress response may be involved in the exacerbation of negative emotions associated with drug withdrawal and stimulant-induced psychosis. 相似文献
3.
Previous studies of conventional tricyclic and non-tricyclic antidepressants have suggested that a number of these drugs display considerable pharmacological activity at 5-HT2C receptors in the brain. There is evidence that 5-HT2C receptors are involved in the control of the activity of the central dopaminergic system. Therefore, the effects of amitriptyline (5 mg/kg and 10 mg/kg i.p.) and of the atypical antidepressant mianserin (2.5 mg/kg and 5 mg/kg i.p.) were studied on the extracellular concentration of dopamine (DA) in the nucleus accumbens of chloral hydrate-anesthetized rats, using intracerebral microdialysis. Amitriptyline and mianserin significantly increased DA release (+31.1 +/- 7.9% and +33.6 +/- 4.3%, respectively) at the higher doses. In addition, lower doses of mianserin (2.5 mg/kg i.p.) and amitriptyline (5 mg/kg i.p.) blocked the inhibitory action of RO 60-0175 (1 mg/kg i.p.), a selective 5-HT2C receptor agonist, on DA release. The effect of RO 60-0175 (1 mg/kg i.p.) was completely blocked by SB 242084 (2.5 mg/kg i.p.), a selective and powerful 5-HT2C receptor antagonist. Taken together, these data indicate that amitriptyline and mianserin increase DA release in the nucleus accumbens by blocking 5-HT2C receptors. 相似文献
4.
In vivo microdialysis was used to assess the effects of acute and repeated injections of the benzodiazepine midazolam on extracellular
dopamine (DA) concentrations in the nucleus accumbens. Acute administration of midazolam (5 mg/kg, SC) elicited a 22% decrease
in extracellular DA in the nucleus accumbens but failed to affect DA concentrations in the striatum. Similarly, six spaced
intravenous infusions of midazolam, at a dose that has previously been found to support self-administration (0.05 mg per infusion),
produced a 50% decrease in extracellular DA in the nucleus accumbens. In order to assess the effects of subchronic midazolam
injections, two groups of rats were given injections of saline or midazolam (5 mg/kg, SC) for 14 days (two injections per
day). A subsequent challenge injection of midazolam (5 mg/kg) decreased extracellular DA in the nucleus accumbens by 25% in
both groups, indicating that neither tolerance nor sensitization occurred during the repeated drug administration. These experiments
indicate (1) that midazolam differentially affects meso-accumbens and nigrostriatal DA neurons, and (2) that the midazolam-induced
decrease in extracellular DA in the nucleus accumbens is not affected by repeated drug administration. The data further suggest
that the rewarding effects of midazolam are not associated with increased release of DA in the nucleus accumbens. 相似文献
5.
Lecca D Cacciapaglia F Valentini V Gronli J Spiga S Di Chiara G 《Psychopharmacology》2006,184(3-4):435-446
Rationale It has been reported that passive administration of nicotine increases preferentially extracellular dopamine (DA) release
in the shell as compared to that in the core of the nucleus accumbens (NAc). To date, no information is available if this
also applies to active, response-contingent nicotine administration.
Objective This study was aimed to monitor the changes of extracellular DA in the NAc shell and core during active intravenous nicotine
self-administration (SA).
Methods Rats were bilaterally implanted with chronic cannulae and were trained to self-administer nicotine (0.03 mg/kg, i.v.) in single
daily 1-h session for 6 weeks, with an initial fixed ratio (FR) 1 schedule increased to FR 2. Dialysate DA from the NAc shell
and core was monitored before and for 90 min after the start of SA.
Results Significant increases of active nose-pokes over inactive ones were found starting from the 16th SA session. No differences
were found in basal extracellular DA in the NAc subdivisions. Data analysis showed (1) significant increases over basal of
dialysate DA in the NAc subdivisions during nicotine SA, starting from the first week in the shell and from the second week
in the core, (2) preferential increase of extracellular DA during nicotine SA in the shell (24–43%) compared to that in the
core (10–23%) and (3) no change in dialysate DA in NAc subdivisions during extinction.
Conclusions Response-contingent nicotine SA preferentially increases the DA output in the NAc shell as compared to that in the core, independently
from the duration of the nicotine exposure. Increase in NAc DA is strictly related to nicotine action since is not observed
during extinction in spite of active responding. 相似文献
6.
The present study sought to investigate the possibility that the degree of selectivity of dopamine D3/D2 receptor agonists such as quinelorane, 7-hydroxy-2-dipropylaminotetralin (7-OH-DPAT), quinpirole and apomorphine on dopamine D3 over D2 receptor subtypes can be assessed by measuring dopamine transmission in the shell vs. core compartments of the nucleus accumbens by using microdialysis in freely moving rats. Significant reductions in dialysate dopamine levels compared to vehicle-treated animals were observed in the shell of the nucleus accumbens with 3, 10 and 30 microg/kg quinelorane, 100 microg/kg 7-OH DPAT, 25 and 100 microg/kg quinpirole, and 100 microg/kg apomorphine. In the core subregion, significant reductions in dopamine were seen at 10 and 30 microg/kg quinelorane, 25 and 100 microg/kg 7-OH-DPAT, 100 microg/kg quinpirole and 100 microg/kg apomorphine. However, a significant shell/core dichotomy could only be observed in response to the lowest dose of quinelorane (3 microg/kg) with the shell being hyper-responsive compared with the core. The present findings suggest that quinelorane is one of the most selective dopamine D3 receptor agonists based on its ability to target the shell subregion of the nucleus accumbens. 相似文献
7.
Role of muscarinic receptors in the activation of the ventral subiculum and the consequences for dopamine release in the nucleus accumbens 总被引:2,自引:0,他引:2
Emodin (1,3,8-trihydroxy-6-methylanthraquinone) is an active herbal component traditionally used in China for treating various ailments. Emodin exerts antiproliferative effects in many cancer cell lines and the actual molecular mechanism of which is still not clear. Since apoptosis could be a potential mechanism to explain these effects, we tested whether emodin induces cell death in human cervical cancer cells. Our results suggest that emodin exerts antiproliferative effects in human cervical cancer cells. Emodin inhibited DNA synthesis and induced apoptosis as demonstrated by increased nuclear condensation, annexin binding and DNA fragmentation in Bu 25TK cells in the presence of emodin. Moreover, we demonstrate for the first time in human cervical cancer cells that the apoptotic pathway involved in emodin-induced apoptosis is caspase-dependent and presumably through the mitochondrial pathway, as shown by the activation of caspases-3, -9 and cleavage of poly(ADP-ribose) polymerase. 相似文献
8.
The mesoaccumbens dopamine pathway exhibits an enhanced dopaminergic response to a challenge injection of d-amphetamine or cocaine after repeated intermittent exposure to that drug. Much research has focused on the potential role
of this sensitised response in the enhanced propensity of drug-associated stimuli to elicit relapse. However, the amygdala
is acknowledged to play a critical role in stimulus-reward learning, and recent work suggests that the mesoamygdaloid dopamine
pathway exerts a significant influence upon amygdala function. In the present study, rats were administered d-amphetamine (1 mg/kg, IP) or vehicle once per day, for 14 days. After 11 untreated days, a locomotor assay showed that prior
repeated administration of d-amphetamine led to a markedly enhanced locomotor response to 0.5 mg/kg d-amphetamine. There was no effect of d-amphetamine pretreatment upon the response to a novel environment, or to injection with vehicle. Following a total of 14 days
in the home cage, subjects were implanted with microdialysis probes within the amygdala, and for comparison also within the
nucleus accumbens. Baseline and d-amphetamine-stimulated (0.5 mg/kg) levels of extracellular dopamine were assessed for each brain region. Results showed that
baseline levels of dopamine were very similar in sensitised and control animals. By contrast, prior treatment with d-amphetamine enhanced dopamine overflow in response to a challenge with d-amphetamine both in the nucleus accumbens and amygdala. These results indicate that changes in the pattern of dopamine transmission
both in the nucleus accumbens, and the amygdala, accompany the behavioural sensitisation observed after repeated exposure
to d-amphetamine. Hence, an enhanced propensity of drug-associated stimuli to elicit relapse may not depend solely upon changes
relating to the mesoaccumbens dopamine projection.
Received: 24 October 1996/Final version: 28 February 1997 相似文献
9.
Behavioral sensitization and extracellular dopamine responses to amphetamine after various treatments 总被引:6,自引:2,他引:4
The repeated administration of amphetamine (AMPH) results in a pattern of behavioral changes which includes an augmentation
of some behaviors, generally referred to as behavioral sensitization. Some investigators have suggested that an increased
dopamine (DA) response to AMPH challenge may underlie behavioral sensitization, while others have reported behavioral sensitization
in the absence of an enhanced DA response. Because temporal and dosage parameters of the AMPH pretreatment regimen have been
suggested to play a role in the appearance of an enhanced DA response, we utilized a variety of AMPH pretreatment regimens
to assess the relationship between pretreatment dose of AMPH, duration of withdrawal and the DA response in caudate-putamen
and nucleus accumbens to a subsequent AMPH challenge. Under our experimental conditions, behavioral sensitization was observed
after each of these treatments in the absence of an enhanced DA response in either brain region.
Received: 9 October 1996 /Final version: 15 May 1997 相似文献
10.
A variety of studies indicate that CART in the nucleus accumbens (NAcc) is involved in the action of psychostimulants. In order to understand in more detail if and how dopamine is involved in the regulation of CART mRNA in the NAcc, the present studies of individual receptors were performed. The D1 agonist, dihydrexidine, and the D1 antagonist, SCH23,390, were administered separately and in combination to adult male rats; however, no changes were found in CART mRNA as measured by in situ hybridization. The D2/3 agonist, quinpirole, was administered either separately or in combination with the D2 selective antagonist, L741,626, or the D3 selective antagonist, GR103,691. Quinpirole produced a decrease in CART mRNA of up to 43%. This effect was blocked by pretreatment with the D3 antagonist GR103, 691, but not by the D2 antagonist, L741,626. CART peptide levels showed a similar decrement after acute quinpirole. CART mRNA levels in the NAcc of D3 mutant mice were found to be higher than that in wild-type animals, but treating the mutants with quinpirole failed to produce a decrease in CART expression like that observed in wild-type rodents. These findings demonstrate that CART is regulated by dopamine in the NAcc, at least partly by D3 dopamine receptors. 相似文献
11.
Activation of dopamine D-1 receptors with multiple administrations of SKF 38393 significantly increased the level of neurotensin-like immunoreactivity in the striatum and the nucleus accumbens. However, a similar treatment with the D-2 receptor-selective agonist, LY 171555, decreased the same in both structures; when the two drugs were administered concureently, their individual effects were blocked. These results suggest that dopamine D-1 and D-2 receptors antagonistically regulate neurotensin systems of the striatum and nucleus accumbens. On the other hand, blockade of D-2 receptors (with sulpiride) elevated, while D-1 receptors blockade (with SCH 23390) caused no change in the level of neurotensin in both these structures. Dopamine D-1 receptors did not appear to contribute to the sulpiride-mediated effect as concurrent administration of SCH 23390 did not alter the response. 相似文献
12.
Effects of nicotine and mecamylamine-induced withdrawal on extracellular dopamine and acetylcholine in the rat nucleus accumbens 总被引:4,自引:0,他引:4
RATIONALE: Prior research suggests that high levels of acetylcholine (ACh) in the nucleus accumbens (NAc) are associated with aversive states such as morphine withdrawal, but this has not been tested for nicotine withdrawal. OBJECTIVES: The goal was to test the hypothesis that acute nicotine decreases extracellular ACh and increases extracellular dopamine (DA) in the NAc, while withdrawal from nicotine causes an opposite neurochemical imbalance with high extracellular ACh and low DA. METHODS: Rats were prepared with a microdialysis probe in the NAc (primarily the shell region). They received one injection of nicotine (0.5 mg/kg, s.c.) or chronic nicotine (9 mg/kg per day via osmotic minipump). RESULTS: Naive animals receiving acute nicotine showed a mild, significant increase in both ACh (122% of baseline) and DA (124%). After chronic nicotine administration for 7 days, the nicotinic antagonist mecamylamine (1.0 mg/kg, s.c.) precipitated withdrawal with the appearance of somatic signs (teeth chattering and shakes/tremors) and a significant increase in extracellular ACh to 125% of baseline, while extracellular DA decreased to 65%. Control groups receiving saline in place of nicotine or mecamylamine did not show these effects. CONCLUSIONS: Earlier work suggests that the observed release of accumbens ACh and DA in response to acute nicotine administration may be a factor in nicotine-induced suppression of appetite. ACh release during withdrawal, coupled with the decrease in extracellular DA may play a role in the aversive aspects of nicotine withdrawal that contribute to dependency. 相似文献
13.
Previous studies from our laboratory using methylnaloxonium, a hydrophilic antagonist, showed that opiate receptors in the region of the nucleus accumbens are important for the acute reinforcing effects of heroin in non-dependent rats. A similar increased sensitivity to the response disruptive effects of intracerebrally injected methylnaloxonium in opiate dependent rats was observed in a fixed-ratio (FR) baseline of operant behaviors. These results suggest that the same opiate receptors in the region of the nucleus accumbens important for the positive reinforcing stimulus properties of opiates may also be responsible for the response disruptive, aversive stimulus properties of opiate withdrawal. These results also suggest that the neural substrates of some aspects of dependence may be partly related to those of the reinforcing effects of opiates. In particular, it is hypothesized that euphoria and dysphoria induced by opiates may reflect opponent motivational processes operating at a cellular level within the nucleus accumbens. 相似文献
14.
Rationale WIN 55,212-2, a potent cannabinoid receptor 1 agonist, is self-administered by animals to evaluate abuse liability of cannabinoids, but to date no information is yet available about its effects on dopaminergic transmission during active response-contingent administration.Objectives This study monitored the changes of extracellular dopamine (DA) in the nucleus accumbens (NAc) shell and core during active intravenous WIN 55,212-2 self-administration (SA).Methods Rats, implanted with a jugular catheter and bilateral intracerebral chronic cannulae, were trained for 3 weeks to self-administer WIN 55,212-2 (12.5 μg/kg) in single daily 1-h sessions under a fixed ratio 1 (FR 1) schedule, than switched to FR 2 for a further week. During SA sessions, microdialysis assays were performed every 3rd day, and then daily starting from the 13th session. Dialysate DA from the NAc shell and core was monitored before, during, and for 30 min after SA.Results Dialysate DA increased during WIN 55,212-2 SA starting from the 1st week in the NAc shell and on the 2nd week in the core. The increase of dialysate DA in the NAc shell was larger than that in the core on all weeks. Dialysate DA did not change during extinction sessions in spite of active nose poking.Conclusions Response-contingent WIN 55,212-2 SA preferentially increases the NAc shell DA output as compared to that of the core independently from the duration of the WIN 55,212-2 exposure. Increase in NAc DA is strictly related to WIN 55,212-2 actions because it is not observed during extinction despite active responding. 相似文献
15.
Feduccia AA Wang Y Simms JA Yi HY Li R Bjeldanes L Ye C Bartlett SE 《Pharmacology, biochemistry, and behavior》2012,102(2):241-248
Purine compounds, such as caffeine, have many health-promoting properties and have proven to be beneficial in treating a number of different conditions. Theacrine, a purine alkaloid structurally similar to caffeine and abundantly present in Camellia kucha, has recently become of interest as a potential therapeutic compound. In the present study, theacrine was tested using a rodent behavioral model to investigate the effects of the drug on locomotor activity. Long Evans rats were injected with theacrine (24 or 48 mg/kg, i.p.) and activity levels were measured. Results showed that the highest dose of theacrine (48 mg/kg, i.p.) significantly increased locomotor activity compared to control animals and activity remained elevated throughout the duration of the session. To test for the involvement of adenosine receptors underlying theacrine's motor-activating properties, rats were administered a cocktail of the adenosine A1 agonist, N6-cyclopentyladenosine (CPA; 0.1 mg/kg, i.p.) and A2A receptor agonist 2-p-(2-carboxyethyl)phenethylamino-5′-N-ethylcarboxamidoadenosine (CGS-21680; 0.2 mg/kg, i.p.). Pre-treatment with theacrine significantly attenuated the motor depression induced by the adenosine receptor agonists, indicating that theacrine is likely acting as an adenosine receptor antagonist. Next, we examined the role of DA D1 and D2 receptor antagonism on theacrine-induced hyperlocomotion. Both antagonists, D1R SCH23390 (0.1 or 0.05 mg/kg, i.p.) and D2R eticlopride (0.1 mg/kg, i.p.), significantly reduced theacrine-stimulated activity indicating that this behavioral response, at least in part, is mediated by DA receptors. In order to investigate the brain region where theacrine may be acting, the drug (10 or 20 μg) was infused bilaterally into nucleus accumbens (NAc). Theacrine enhanced activity levels in a dose-dependent manner, implicating a role of the NAc in modulating theacrine's effects on locomotion. In addition, theacrine did not induce locomotor sensitization or tolerance after chronic exposure. Taken together, these findings demonstrate that theacrine significantly enhances activity; an effect which is mediated by both the adenosinergic and dopaminergic systems. 相似文献
16.
The effect of long-term treatment (three times daily for 3 weeks) with a behaviorally relevant dose of the benzodiazepine
receptor partial agonist imidazenil (0.5 mg/kg, IP) on basal dopamine release in the nucleus accumbens of freely moving rats
was compared with that of diazepam (3 mg/kg, IP), a benzodiazepine receptor full agonist. Challenge doses of imidazenil and
diazepam decreased the extracellular dopamine concentration in the nucleus accumbens by approximately the same extent in animals
repeatedly exposed to vehicle or to the respective drug. Moreover, the abrupt discontinuation of long-term treatment with
diazepam or imidazenil failed to affect basal dopamine release in this brain area during the first 5 days of withdrawal. In
contrast, administration of the benzodiazepine receptor antagonist flumazenil (4 mg/kg, IP) elicited a marked increase (95
or 60%) in dopamine release in the nucleus accumbens 6h after withdrawal of diazepam or imidazenil, respectively. Flumazenil
induced a similar but smaller effect (50% increase) 5 days after diazepam withdrawal but had no effect 5 days after discontinuation
of imidazenil treatment. The resultssupport an involvement of the mesoaccumbens dopaminergic neurons in the withdrawal syndrome
precipitated by flumazenil and allow further differentiation of benzodiazepine receptor partial and full agonists with respect
to dependence liability of dopaminergic neurons in the nucleus accumbens.
Received: 20 June 1996 / Final version: 27 November 1996 相似文献
17.
Rationale Attentional deficits are thought to be critically involved in the development of positive symptoms in schizophrenia. The present experiment tests the general hypothesis that sensitization of the mesolimbic dopaminergic system contributes to the attentional deficits in schizophrenia.Objectives The present study assessed attentional performance following administration of an escalating amphetamine regimen and subsequent challenge amphetamine administration in rats.Methods Rats were trained to perform a two-lever sustained attention task that involved discrimination of visual signals and no signal presentation. After reaching criterion, subjects were assigned to receive escalating amphetamine or saline. Attentional performance was assessed immediately following escalating amphetamine, following challenge amphetamine administration (1.0 mg/kg) to amphetamine-pretreated rats, and for 3 days after the challenge session. At the end of this experiment, a dose-response study was conducted with saline-pretreated rats to confirm the appropriateness of the challenge dose.Results Amphetamine-pretreated animals demonstrated a transient increase in errors on non-signal trials following escalating amphetamine administration. The latency to press a lever was decreased during and after challenge amphetamine administration. Administration of 1.0 mg/kg amphetamine did not alter accuracy of amphetamine-pretreated animals or of saline-pretreated animals in the dose-response experiment.Conclusions Prior escalating amphetamine administration transiently disrupted attention, increasing incorrect claims for a signal on trials when no signal was presented. The present data support the existing literature that escalating amphetamine regimens may be useful to model the attentional deficits that contribute to the psychotic symptoms in schizophrenia. 相似文献
18.
Junji Ichikawa Toshihide Kuroki Herbert Y. Meltzer 《European journal of pharmacology》1998,350(2-3):159-164
The effect of chronic treatment with the tricyclic antidepressant drug, imipramine (10 mg/kg per day), the selective serotonin (5-HT) reuptake inhibitor, fluoxetine hydrochloride (10 mg/kg per day), and vehicle, in drinking water for 24–28 days followed by 3–5 days withdrawal, on extracellular dopamine levels was studied in rat nucleus accumbens by in vivo microdialysis. Basal extracellular dopamine levels in the nucleus accumbens were increased after chronic imipramine (12.7±1.5 fmol/20 μl per 30 min, P=0.019), and moderately decreased after chronic fluoxetine (6.5±0.6, P=0.047), as compared to the vehicle controls (9.1±0.7), determined by one-way analysis of variance (ANOVA). Repeated measure ANOVA indicated that the -amphetamine sulfate (0.5 mg/kg, s.c.)-induced increase in extracellular dopamine levels in the nucleus accumbens was potentiated after chronic imipramine (P=0.002), but unchanged after chronic fluoxetine (P=0.83). The difference in the effect of amphetamine could be influenced by the significant differences in basal levels. However, these results were also confirmed by analysis of the net area under the curve (net-AUC) for a 180-min period (six samples): for chronic imipramine (337±45 fmol/180 min, P=0.005) and chronic fluoxetine (249±38, P=0.57), as compared to the vehicle controls (178±29), determined by one-way ANOVA. We suggest that the effect of treatment with these agents on mesolimbic dopamine is unlikely to be involved in their shared antidepressant action, but may be relevant to other aspects of the therapeutic profile of these two drugs, e.g. the switch into mania which is more common after treatment with imipramine than fluoxetine and exacerbation of positive symptoms in patients with schizophrenia or schizoaffective disorder. 相似文献
19.
George G. Nomikos Athanasios P. Zis Geert Damsma Hans C. Fibiger 《Psychopharmacology》1991,105(2):230-238
There is accumulating evidence that chronic electroconvulsive shock (ECS) can increase the functional output of central dopaminergic systems. The present experiments investigated the effects of acute and chronic ECS on interstitial concentrations of dopamine (DA) in the nucleus accumbens (NAC) using in vivo microdialysis in awake freely moving rats. ECS (150 V, 0.75 s) increased interstitial concentrations of DA, DOPAC and HVA to approximately 130% of baseline values. The magnitude of the ECS-induced increase in DA was not affected by chronic ECS. In contrast, the response of the DA metabolites was attenuated in the chronic ECS group. Chronic ECS did not influence apomorphine (25 µg/kg, SC)-induced decreases in extracellular concentrations of DA or its metabolites in the NAC, thus providing no support for the hypothesis that chronic ECS produces subsensitivity of DA autoreceptors.d-Amphetamine (1.5 mg/kg SC)-induced increases in extracellular DA were significantly prolonged in the NAC of the chronic ECS group. In accordance with previous reports, the locomotor stimulant effects ofd-amphetamine were also enhanced in the chronic ECS group. These data provide further evidence that chronic ECS can increase certain behavioral and neurochemical indices of meso-accumbens DA function. 相似文献
20.
Cano-Cebrián MJ Zornoza-Sabina T Guerri C Polache A Granero L 《Naunyn-Schmiedeberg's archives of pharmacology》2003,368(4):324-327
Recently, we have shown that acamprosate is able to modulate extracellular dopamine (DA) levels in the nucleus accumbens (NAc) and may act as an antagonist of N-methyl-D-aspartate (NMDA) receptors. Neurochemical studies show that chemical stimulation (using NMDA) of the ventral subiculum (vSub) of the hippocampus produces robust and sustained increases in extracellular DA levels in the NAc, an effect mediated through ionotropic glutamate (iGlu) receptors. The present study examines whether acamprosate locally infused in the NAc of rats could block or attenuate the increase in NAc extracellular DA elicited by chemical stimulation (with 5 mM NMDA) of the ventral subiculum of the hippocampus. The stimulation of the vSub during perfusion of artificial cerebrospinal fluid in NAc induced a significant and persistent increase in NAc DA levels. Reverse dialysis of 0.05 mM acamprosate in NAc blocked the increase in DA evoked by the chemical stimulation of the vSub. These data support the possibility that the antagonism at the NMDA receptors in NAc can explain, at least in part, the mechanism of action of this drug. 相似文献