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1.
BACKGROUND AND PURPOSE
Intracerebroventricularly injected tachykinin NK3 receptor (R) antagonists normalize mean arterial blood pressure (MAP) in spontaneously hypertensive rats (SHR). This study was pursued to define the role played by NK3R located on dopamine neurones of the ventral tegmental area (VTA) in the regulation of MAP in SHR.EXPERIMENTAL APPROACH
SHR (16 weeks) were implanted permanently with i.c.v. and/or VTA guide cannulae. Experiments were conducted 24 h after catheterization of the abdominal aorta to measure MAP and heart rate (HR) in freely behaving rats. Cardiovascular responses to i.c.v. or VTA-injected NK3R agonist (senktide) and antagonists (SB222200 and R-820) were measured before and after systemic administration of selective antagonists for D1R (), D2R (raclopride) or non-selective D2R (haloperidol), and after destruction of the VTA with ibotenic acid. SCH23390KEY RESULTS
I.c.v. or VTA-injected SB222200 and R-820 (500 pmol) evoked anti-hypertension, which was blocked by raclopride. Senktide (10, 25, 65 and 100 pmol) elicited greater increases of MAP and HR when injected in the VTA, and the cardiovascular response was blocked by R-820, and haloperidol. VTA-injected SB222200 prevented the pressor response to i.c.v. senktide, and vice versa, i.c.v. senktide prevented the anti-hypertension to VTA SB222200. Destruction of the VTA prevented the pressor response to i.c.v. senktide and the anti-hypertension to i.c.v. R-820. SCH23390CONCLUSIONS AND IMPLICATIONS
The NK3R in the VTA is implicated in the maintenance of hypertension by increasing midbrain dopaminergic transmission in SHR. Hence, this receptor may represent a therapeutic target in the treatment of hypertension. 相似文献2.
Spinal cord excitation was induced in mice by morphine and the effects of dopamine D1 and D2 receptor antagonists on the Straub tail reaction were investigated. The dopamine D2 receptor antagonist, sulpiride (25-100 mg/kg i.p.), or haloperidol (0.25-1.0 mg/kg dose dependently inhibited the Straub tail reaction induced by subcutaneously injected morphine. A low dose of apomorphine (50 micrograms/kg s.c.) also reduced the Straub tail reaction. The dopamine D1 receptor antagonist, SCH-23390 (25-100 micrograms/kg i.p.), had no significant effect. Sulpiride (50 mg/kg i.p.) significantly inhibited the Straub tail reaction induced by intrathecally injected morphine (6 microgram/mouse). Intrathecal injection of apomorphine (12.5-25 micrograms/mouse) induced the Straub tail reaction dose dependently. The Straub tail reaction induced by intrathecally injected apomorphine was significantly inhibited by sulpiride. SCH-23390 had no significant effect on the Straub tail reaction induced by intrathecally injected morphine or apomorphine. These results support the proposal that the dopamine response involved in the Straub tail reaction is mediated by postsynaptic dopamine D2 receptors in the spinal cord of mice. 相似文献
3.
Inna Ruiz-Salinas Abimael González-Hernández Guadalupe Manrique-Maldonado Bruno A. Marichal-Cancino Alain H. Altamirano-Espinoza Carlos M. Villalón 《Naunyn-Schmiedeberg's archives of pharmacology》2013,386(5):393-403
We have recently reported that quinpirole (a D2-like receptor agonist) inhibits the vasopressor sympathetic outflow in pithed rats via sympatho-inhibitory D2-like receptors. Since D2-like receptors consist of D2, D3 and D4 receptor subtypes, this study investigated whether these subtypes are involved in the above quinpirole-induced sympatho-inhibition by using antagonists of these receptor subtypes. One hundred fifty-six male Wistar rats were pithed and prepared for preganglionic spinal (T7–T9) stimulation of the vasopressor sympathetic outflow. This approach resulted in frequency-dependent vasopressor responses which were analysed before and during i.v. continuous infusions of either saline (0.02 ml/min) or quinpirole (1 μg/kg.min) in animals receiving i.v. bolus injections of vehicle [saline or dimethyl sulfoxide (DMSO)] or the antagonists L-741,626 (D2), nafadotride or SB-277011-A (both D3) as well as L-745,870 (D4). Quinpirole inhibited the sympathetically-induced vasopressor responses. This sympatho-inhibition was (a) unaltered after 1 ml/kg saline, DMSO or 100 and 300 μg/kg L-741,626; (b) markedly blocked and abolished by, respectively, 30 and 100 μg/kg nafadotride or 100 and 300 μg/kg SB-277011-A and (c) slightly blocked after 30 and 100 μg/kg L-745,870, but 300 μg/kg L-745,870 produced no blockade whatsoever. Except for 300 μg/kg L-741,626 or 300 μg/kg L-745,870, the doses of the above compounds failed to modify per se the sympathetic vasopressor responses. The inhibition of the vasopressor sympathetic outflow induced by 1 μg/kg.min quinpirole in pithed rats is predominantly mediated by dopamine D3 and, to a lesser extent, by D4 receptor subtypes, with no evidence for the involvement of the D2 subtype. 相似文献
4.
The objective of this study was to determine whether the development of behavioral sensitization to cocaine could be prevented by either D1 or D2 selective dopamine receptor antagonists. Male Wistar rats were treated daily for 7 days with either cocaine (15 mg/kg, IP) or vehicle in combination with the D1 dopamine antagonist SCH 23390 (0.3 mg/kg, SC), the D2 dopamine antagonist sulpiride (100 mg/kg, IP), or vehicle. After the daily injections, the rats were tested for locomotor activity in photocell arenas. Twenty-four hours after the last pre-exposure test session, all rats were given a challenge injection of cocaine (15 mg/kg, IP) and tested for activity. Cocaine treatments produced a greater relative increase in locomotor activity with repeated exposure (i.e. sensitization). Moreover, this increase in cocaine-induced locomotor activity was attenuated by both SCH 23390 and sulpiride. In contrast, neither sulpiride nor SCH 23390 blocked the development of behavioral sensitization to cocaine. That is, rats pretreated with sulpiride or SCH 23390 and cocaine did not differ from rats pre-exposed only to cocaine when given a cocaine challenge injection. These results suggest that behavioral sensitization to cocaine may develop through either D1 or D2 dopamine receptor stimulation or possibly through stimulation of some non-dopaminergic receptor.Portions of this paper were presented at the 1992 Society for Neuroscience meetings, Anaheim, Cal., USA 相似文献
5.
Dopamine antagonist effects on locomotor activity in naive and ethanol-treated FAST and SLOW selected lines of mice 总被引:1,自引:0,他引:1
The FAST and SLOW lines of mice are being selectively bred in replicate for differential sensitivities to the locomotor activating effects of ethanol. Whereas FAST-1 and FAST-2 mice are stimulated by 2.0 g/kg ethanol, SLOW-1 and SLOW-2 mice are not stimulated, and are often depressed, by this dose. The dopamine antagonists, SCH-23390 (D1) and raclopride (D2), produced dose-dependent decreases in the locomotor activity of EtOH-naive mice of both lines and replicates; however, FAST and SLOW mice were not differentially sensitive to these effects. The absence of a line difference in activity response to the dopamine antagonists suggests that dopamine receptor function has not been altered by selective breeding for differences in sensitivity to the stimulant effects of ethanol. The ethanol-stimulated activity of FAST-1 and FAST-2 mice was decreased by administration of the dopamine antagonists, haloperidol and raclopride, at doses that had no effect on basal locomotor activity. SCH-23390 decreased ethanol-stimulated activity of FAST-1, but not FAST-2 mice. The ethanol-induced activity changes of SLOW mice were generally unaffected by antagonist administration. These results suggest a role for dopaminergic systems in mediating ethanol-stimulated activity in selectively bred FAST mice. Coadministration of SCH-23390 and raclopride decreased ethanol-induced activation to a greater degree than either drug alone, further suggesting that both D1 and D2 receptor systems contribute to the full expression of the ethanol stimulant response.This work was supported by the Department of Veterans Affairs, by NIAAA grants AA06498 and AA08621 (J.C.C. and T.J.P.), and by an N. L. Tartar Research Fellowship from the Medical Research Foundation of Oregon (E.H.S.). A portion of this work was completed in partial fulfillment of the requirements for Master of Science degree, Department of Medical Psychology, Oregon Health Sciences University (E.H.S.). 相似文献
6.
Peter Salmi Kristina Malmgren Torgny H. Svensson Sven Ahlenius 《Naunyn-Schmiedeberg's archives of pharmacology》1998,357(6):593-599
In d-amphetamine-treated (4.0 mg kg–1 s.c.) rats the selective dopamine D1 and D2/3 receptor antagonists SCH-23390 (2.5–20.0 μg kg–1 s.c.) and raclopride (12.5–100.0 μg kg–1 s.c.), respectively, produced a biphasic pattern of effects on forward locomotion, as observed in an open-field arena (≈0.5
m2). Thus, at the low doses of SCH-23390 (2.5–10.0 μg kg–1) or raclopride (12.5–50.0 μg kg–1), there was a statistically significant increase in forward locomotion, followed by suppression of the behavior at the higher
doses. The SCH-23390-induced (5.0 μg kg–1) stimulation of forward locomotion was partially antagonized by concomitant raclopride treatment (12.5–25.0 μg kg–1) and the corresponding raclopride-induced (12.5 μg kg–1) stimulation was fully antagonized by treatment with SCH-23390 (2.5–5.0 μg kg–1). Furthermore, the SCH-23390- or raclopride-induced stimulation of forward locomotion was also antagonized by treatment with
the α1-adrenoceptor antagonist prazosin (1.0 mg kg–1 s.c.). These observations suggest that under conditions of an increased general tone at brain dopamine receptors, there is
a mutual inhibitory synergy between dopamine D1 and D2/3 receptors.
Received: 21 July 1997 / Accepted: 6 March 1998 相似文献
7.
Sufficient evidence exists for the inclusion of the ventral pallidum (VP) into the category of a dopaminoceptive brain region. The effects of inhibiting dopamine D(1)- or D(2)-like receptors in the VP on (a) ethanol intake and (b) extracellular levels of dopamine, were investigated in the alcohol-preferring (P) rat. The D(1)-like antagonist, SCH-23390, and the D(2)-like antagonist, sulpiride (0.25-2 microg/0.5 microl) were bilaterally injected into the VP and ethanol (15%, v/v) intake was assessed in a 1 h limited access paradigm. The results indicate that microinjections of sulpiride significantly increased ethanol consumption (65% increase at the 2.0 microg dose). Whereas the D(1) antagonists SCH-23390 tended to decrease ethanol intake, the effect was not statistically significant. In a separate group of rats, reverse microdialysis of sulpiride and SCH-23390 (10-200 microM) were conducted in the VP of P rats. Local perfusion of only the 200 microM sulpiride dose significantly increased the extracellular levels of dopamine (maximal increase: 250% of baseline). On the other hand, local perfusion of SCH-23390 (10-200 microM) dose dependently increased the extracellular levels of dopamine 180-640% of baseline. Overall, the results of this study suggest that (a) tonic activation of D(2) postsynaptic receptors in VP imposes a limit on ethanol intake in the P rat; (b) there are few D(2) autoreceptors functioning in the VP; (c) there is tonic D(1)-like receptor mediated inhibitory feedback regulation of VP-dopamine release. 相似文献
8.
Evidence for regulation of body temperature in rats by dopamine D2 receptor and possible influence of D1 but not D3 and D4 receptors 总被引:3,自引:0,他引:3
The dopamine D3 receptor agonist PD 128907 decreased body temperature in the rat. The selective dopamine D3 and D4 receptor antagonists, A-437203 and L-745,870, respectively, did not prevent this effect. In contrast, PD 128907-induced hypothermia was antagonized by SCH 23390, a selective D1 receptor antagonist, and by L-741,626, a selective D2 receptor antagonist. Moreover, the selective D2 receptor agonist trihydroxy-N-n-propylnoraporphine (TNPA) elicited a robust hypothermia which was prevented by pretreatment with L-741,626 but not by A-437203. In agreement with previous data obtained in D3 knock-out mice, present results suggest that D2 rather than D3 receptors mediate dopamine receptor agonist-induced hypothermia in rats. In addition, it appears that both D1 and D2 receptors may be involved in a cooperative manner. 相似文献
9.
Hideki Ono Yui Iwajima Yuko Nagano Kaori Chazono Yasuhiro Maeda Masahiro Ohsawa Shohei Yamamoto 《Basic & clinical pharmacology & toxicology》2013,113(1):25-30
Oseltamivir, an anti‐influenza virus drug, has strong antipyretic effects in mice (Biological and Pharmaceutical Bulletin, 31, 2008, 638) and patients with influenza. In addition, hypothermia has been reported as an adverse event. The prodrug oseltamivir is converted to oseltamivir carboxylate (OC), an active metabolite of influenza virus neuraminidase. In this study, core body temperature was measured in mice, and oseltamivir and OC were administered intracerebroventricularly (i.c.v.) or intraperitoneally (i.p). Low i.c.v. doses of oseltamivir and OC dose‐dependently produced hypothermia. Zanamivir (i.c.v.), another neuraminidase inhibitor, did not produce hypothermia. These results suggested that the hypothermic effects of oseltamivir (i.p. and i.c.v.) and OC (i.c.v.) are not due to neuraminidase inhibition. OC (i.p.) did not lower body temperature. Although mecamylamine (i.c.v.) blocked the hypothermic effect of nicotine‐administered i.c.v., the hypothermic effects of oseltamivir and OC (i.c.v.) were not blocked by mecamylamine (i.c.v.). The effect of oseltamivir (i.p.) was markedly increased by s.c.‐pre‐administered mecamylamine and also hexamethonium, a peripherally acting ganglionic blocker, suggesting their potentiating interaction at peripheral sites. The hypothermic effect of nicotine (i.c.v.) was decreased by lower doses of oseltamivir (i.c.v.), suggesting the anti‐nicotinic action of oseltamivir. These results suggest that oseltamivir (i.p.) causes hypothermia through depression of sympathetic temperature regulatory mechanisms via inhibition of nicotinic receptor function and through unknown central mechanisms. 相似文献
10.
Pretreatment with ineffective doses of the D1 antagonist SCH23390 but not the D2 antagonist sulpiride reduced hyperactivity induced by nicotine in mice habituated to the test cage. On the other hand, the D1 and D2 antagonists were ineffective in blocking nicotine-induced hypoactivity in naive mice. Finally, SCH23390 and sulpiride did not block the antinociception induced by nicotine. Our data indicate that the dopamine receptors D1 and D2 are not involved in all the central effects of nicotine in mice, but seems to be a substrate for locomotor activation induced by nicotine under specific experimental conditions. 相似文献
11.
Bruce A. Mattingly James K. Rowlett Jamison T. Graff Billie Jo Hatton 《Psychopharmacology》1991,105(4):501-507
The objective of the present study was to determine whether the development of behavioral sensitization to apomorphine could be blocked by either D1 or D2 selective dopamine antagonists. In three experiments, male rats received 10–21 daily injections of a selective D1 (SCH 23390; 0 or 0.5 mg/kg IP) or D2 (sulpiride; 0, 30, or 100 mg/kg IP) antagonist followed by an apomorphine (0 or 1.0 mg/kg SC) injection. In two experiments, the rats were tested for locomotor activity in photocell arenas after the daily injections. In all experiments, the rats were tested for sensitization to apomorphine following the training phase. The results indicated that apomorphine produced a progressively greater increase in locomotor activity with each injection, and this apomorphine-induced increase in activity was completely blocked by both sulpiride and SCH 23390 treatments. However, although both sulpiride and SCH 23390 blocked apomorphine-induced activity, only SCH 23390 injections prevented the development of sensitization to apomorphine. That is, rats pretreated with sulpiride and apomorphine displayed significant sensitization when subsequently tested with a challenge dose of apomorphine alone. These findings suggest that the development of behavioral sensitization to apomorphine is related specifically to the stimulation of dopamine D1 receptors.Portions of this paper were presented at the 1990 Society for Neuroscience meetings, St. Louis, MO, USA 相似文献
12.
Rosenzweig-Lipson S Sabb A Stack G Mitchell P Lucki I Malberg JE Grauer S Brennan J Cryan JF Sukoff Rizzo SJ Dunlop J Barrett JE Marquis KL 《Psychopharmacology》2007,192(2):159-170
Rationale Identification of behaviors specifically mediated by the dopamine D2 and D3 receptors would allow for the determination of
in vivo receptor selectivity and aide the development of novel therapeutics for dopamine-related diseases.
Objectives These studies were aimed at evaluating the specific receptors involved in the mediation of D2/D3 agonist-induced yawning and
hypothermia.
Materials and methods The relative potencies of a series of D2-like agonists to produce yawning and hypothermia were determined. The ability of
D3-selective and D2-selective antagonists to inhibit the induction of yawning and hypothermia were assessed and a series of
D2/D3 antagonists were characterized with respect to their ability to alter yawning induced by a low and high dose of PD-128,907
and sumanirole-induced hypothermia.
Results D3-preferring agonists induced yawning at lower doses than those required to induce hypothermia and the D2-preferring agonist,
sumanirole, induced hypothermia at lower doses than were necessary to induce yawning. The rank order of D3 selectivity was
pramipexole > PD-128,907 = 7-OH-DPAT = quinpirole = quinelorane > apomorphine = U91356A. Sumanirole had only D2 agonist effects.
PG01037, SB-277011A, and U99194 were all D3-selective antagonists, whereas haloperidol and L-741,626 were D2-selective antagonists
and nafadotride’s profile of action was more similar to the D2 antagonists than to the D3 antagonists.
Conclusions D3 and D2 receptors have specific roles in the mediation of yawning and hypothermia, respectively, and the analysis of these
effects allow inferences to be made regarding the selectivity of D2/D3 agonists and antagonists with respect to their actions
at D2 and D3 receptors. 相似文献
13.
Four rhesus monkeys were trained to discriminate the effect of apomorphine (0.1 mg/kg IM) from that of saline injections. The discriminative stimulus (DS) effect of apomorphine generalized to the dopamine D2 receptor agonist quinpirole. The D1 dopamine receptor agonist SKF 38393 elicited responses only on the saline-appropriate lever. Stimulus generalization of the dopamine autoreceptor agonist 3-PPP exhibited stereospecificity favoring the (+) over the (-) isomer. d-Amphetamine, phencyclidine, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), and clonidine did not share the DS effect of apomorphine. The D2-selective antagonists sulpiride and metoclopramide reversed both the DS effect and the response rate reduction produced by the training dose of apomorphine. Chlorpromazine and the D1 antagonist Sch 23390 also antagonized the DS effect, but the antagonism was accompanied by a further rate reduction. Haloperidol and clozapine antagonized the DS effect incompletely. The DS effect produced by apomorphine in this study appears to be mediated predominantly by post-synaptic D2 receptor activation, with contribution also from the D1 receptor. 相似文献
14.
Blessing WW 《Psychopharmacology》2005,181(3):518-528
Rationale Clozapine inhibits sympathetic outflow to the cutaneous vascular bed. Clozapine reverses hyperthermia and cutaneous vasoconstriction
induced by 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy) or by lipopolysaccharide (LPS). Clozapine also reverses cutaneous
vasoconstriction elicited by exposure to cold. These actions distinguish clozapine from haloperidol. Clozapine could also
inhibit sympathetic cutaneous vasomotor alerting responses (SCVARs), vasoconstrictor episodes that reflect emotional/psychological
function, and this property might also distinguish clozapine from haloperidol.
Objectives Experiments in rats determined whether clozapine and haloperidol inhibit SCVARs, and whether SR46349B (a 5HT2A receptor antagonist), 8-OH-DPAT (a 5-HT1A agonist), L741,626 (a dopamine D2 antagonist) or SCH23390 (a dopamine D1 antagonist) have clozapine-like effects on SCVARs.
Methods Mean level and pulse amplitude of the tail artery Doppler flow signal were recorded in conscious freely moving rats before
and after alerting stimuli (e.g. tapping the cage), and expressed as a SCVAR index (fall to zero flow implies SCVAR index
of 100%, no fall implies 0%).
Results Clozapine (0.0625–1.0 mg/kg, s.c.) dose-dependently increased resting tail blood flow. After 1 mg/kg, the SCVAR index was
18±1%, compared with 83±2% after vehicle. SR46349B (0.01–1.0 mg/kg) and 8-OH-DPAT (0.25 mg/kg) had similar but less potent
effects on cutaneous blood flow and on SCVARs. Haloperidol (0.005–0.5 mg/kg) and L741,626 (1 mg/kg) had no or little effect
on these variables. SCH23390 mildly inhibited SCVARs.
Conclusions Clozapine, but not haloperidol, increases resting cutaneous blood flow and decreases SCVARs. Antagonism at 5-HT2A receptors and agonism at 5-HT1A receptors could contribute to these actions. 相似文献
15.
《European Journal of Pharmacology: Molecular Pharmacology》1992,225(1):1-5
Incubation of cultured rat glomerular mesangial cells with dopamine caused an increasein cyclic AMP formation in a concentration-dependent manner (Ka apparent 2.2 μM). The selective dopamine D1 receptor agonists, fenoldopam, SKF 38393 and (±)-2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene (6,7-ADTN) also produced concentration-dependent increases in cyclic AMP with mean Ka apparent values of 0.04 μM, 0.02 μM and 1.02 μM, respectively. Although fenoldopam and SKF 38393 were more potent than dopamine, they were partial agonists with efficacies, relative to dopamine, of approximately 60 and 35%, respectively. The dopamine analogue, 6,7-ADTN, in contrast, behaved as a full agonist. Dopamine-stimulated cAMP formation was inhibited in a concentration-dependent manner by the D1-selective antagonist, SCH 23390, with a Ki of 0.06 nM. In contrast, the D2-selective antagonist, domperidone was four orders of magnitude less potent than SCH 23390, having a Ki of 2072 nM. In addition, SCH 23388, the stereoisomer of SCH 23390, was observed to be two orders of magnitude less potent than SCH 23390, indicating the stereoselective nature of the receptor. The potency series for the selective agonists and antagonists is the same as that described, using identical experimental conditions, for the D1 receptor expressed by a cell line of central origin confirming that the peripheral DA1 and the central D1 dopamine receptor are pharmacologically similar. 相似文献
16.
Peter Jenner Martin D. Hall Kamala Murugaiah Nadia Rupniak Andreas Theodorou C.David Marsden 《Biochemical pharmacology》1982,31(3):325-328
Administration of sulpiride (2 × 100 mg/kg i.p.) or haloperidol (5 mg/kg i.p.) to rats for 3 weeks with subsequent withdrawal for 3 or 4 days induced cerebral dopamine receptor supersensitivity. Apomorphine-induced stereotyped behaviour after drug withdrawal was enhanced by pretreatment with either haloperidol or sulpiride both of which increased the number of specific striatal binding sites (Bmax) for [3H]spiperone, [3H]N,n-propylnorapomorphine and [3H]sulpiride. Neither drug altered the dissociation constant (KD) for the ligand binding assays. Striatal dopamine sensitive adenylate cyclase activity was unaltered by such a pretreatment with either haloperidol or sulpiride. The data show that sulpiride, like haloperidol, is capable of inducing behavioural and biochemical supersensitivity of cerebral dopamine receptors. 相似文献
17.
Daniel E. Casey 《Psychopharmacology》1992,107(1):18-22
The ability of dopamine D1 antagonists to produce acute extrapyramidal syndromes (EPS) in nonhuman primates is unclear. Some studies in monkeys show that D1 antagonists produce acute dystonia, whereas other studies do not report these effects. The central issues that have yielded conflicting results revolve around prior treatment status (neuroleptic-naive versus neuroleptic sensitized) and route of administration (oral versus parenteral). In this study, separate groups of neuroleptic drug-naive cebus monkeys were tested once weekly with intramuscularly administered SCH 23390, a D1 antagonist, or haloperidol, a D2 antagonist, across a dose range of 0.01–0.25 mg/kg, and a saline control. Both active drugs, but not saline, produced clinically identical syndromes of acute dystonia and bradykinesia, though haloperidol induced higher symptom scores over a longer duration. Sedation and locomotor activity were unchanged by SCH 23390, but decreased with haloperidol. Factors regarding acute EPS liability in nonhuman primate models and clinical implications in man are discussed. 相似文献
18.
SHIGETO YAMADA TOSHIHIRO TAKAKI HIDEYASU YOKOO MASATOSHI TANAKA 《The Journal of pharmacy and pharmacology》1995,47(3):259-262
The effects of dopamine-receptor antagonists on electrically-evoked dopamine release were compared in the nucleus accumbens and striatal slices of rats. (-)-Sulpiride induced a concentration-dependent increase in the evoked dopamine release from both regions, the increase in the nucleus accumbens being significantly greater than that in the striatum. Clozapine also increased evoked dopamine release from the nucleus accumbens, but not from the striatum. The haloperidol-induced increase in evoked dopamine release from the nucleus accumbens was less than that from the striatum. These findings indicate that, in terms of dopamine transmission, (-)-sulpiride and clozapine, but not haloperidol, predominantly affect the nucleus accumbens rather than the striatum. We have previously reported that the contribution of D3 receptors to the regulation of dopamine release from dopamine nerve terminals is much greater in the nucleus accumbens than that in the striatum. (-)-Sulpiride and clozapine have relatively higher affinity for D3 receptors than does haloperidol. The regional differences in responsiveness of dopamine release to dopamine antagonists could be due to the different affinities to D2 or D3 receptors of the dopamine antagonists. 相似文献
19.
Maria Grazia Zizzo Flavia Mulè Mariangela Mastropaolo Rosa Serio 《Pharmacological research》2010,61(5):371-378
Since the role of dopamine in the bowel motility is far from being clear, our aim was to analyse pharmacologically the effects of dopamine on mouse ileum contractility. Contractile activity of mouse ileum was examined in vitro as changes in isometric tension. Dopamine caused a concentration-dependent reduction of the spontaneous contraction amplitude of ileal muscle up to their complete disappearance. SCH-23390, D1 receptor antagonist, which per se increased basal tone and amplitude of spontaneous contractions, antagonized the responses to dopamine, whilst sulpiride or domperidone, D2 receptor antagonists, were without effects. The application of both D1 and D2 antagonists had additive effects. SKF-38393, D1 receptor agonist, mimicked dopamine-induced effects. Dopamine responses were insensitive to tetrodotoxin, atropine, nitric oxide synthase inhibitor or adenosine receptor antagonists, but they were reduced by adenylyl cyclase inhibition or apamin. Dopamine at a concentration which did not cause a significant reduction of phasic contractions inhibited the cholinergic contractions in response to field stimulation. SCH-23390 per se induced an increase of the neural cholinergic contraction and antagonized the dopamine effects, whilst sulpiride or domperidone did not. The application of D1 and D2 antagonists had additive effects. In conclusion, mouse ileum is under basal inhibitory control by dopamine, through D1 receptor activation, linked to adenylyl cyclase and activation of apamin-sensitive potassium channels. An agonistic interaction of the dopamine receptor subtypes in the regulation intestinal contractility has being also highlighted. This study would provide new insight on the pharmacology of the modulation of the gastrointestinal contractility by dopamine. 相似文献
20.
The efficacy ofd-amphetamine to support a selective bilateral intra-accumbens self-administration response was examined. Bilateral intra-accumbens infusions ofd-amphetamine were made contingent upon the acquisition of a lever-pressing response. Two identical levers were available within the operant chamber. Depression of the drug lever resulted in the intra-accumbens delivery of 1 µgd-amphetamine; responses upon the second, control lever were recorded but had no programmed consequences. Animals were not primed with non-contingent infusions ofd-amphetamine at any time during these experiments. Nonetheless, animals readily acquired a selective response upon the drug lever. Removal of thed-amphetamine moiety from the infusate resulted in a large decline in responding, and the abolition of the selectivity of the response for the drug lever. Adulteration of the infusate with either the D1 dopamine receptor antagonist SCH-23390 or the D2 dopamine receptor antagonist sulpiride enhanced the rate of response selectively upon the drug lever. Reductions in the dose ofd-amphetamine also increased the rate of response. The effect of co-adulteration of the infusate with both SCH-23390 and sulpiride together was purely additive. The implications of these data for the methodology of intracranial drug self-administration, and the relationship between D1 and D2 dopamine receptors within the nucleus accumbens are discussed. 相似文献