Discriminative stimulus properties of S32504, a novel D3/D2 receptor agonist and antiparkinson agent, in rats: attenuation by the antipsychotics, aripiprazole, bifeprunox, N-desmethylclozapine, and by selective antagonists at dopamine D2 but not D3 receptors

Millan, Mark J.; Iob, Loretta; Peglion, Jean‐Louis; Dekeyne, Anne

doi:10.1007/s00213-006-0567-0

Cited by 14 publications

(15 citation statements)

References 78 publications

(156 reference statements)

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“…Consistent with our findings, PG01037 has been found to localize primarily in D3-rich brain regions as determined by pharmacological magnetic resonance imaging (Grundt et al, 2007b) and selectively attenuate the D3-mediated component of quinpirole-induced yawning in rats (Baladi et al, 2010). Unlike PG01037, L-741626 attenuated the cocaine-like DS effects of both sumanirole and PD128907, suggesting less selective effects consistent with previous studies in which L-741626 attenuated the DS effects of another D3 agonist, S32504 [(ϩ)-trans-3,4,4a,5,6, 10b-hexahydro-9-carbamoyl-4-propyl-2H-naphth[1,2-b]-1,4-oxazine] (Millan et al, 2007). Given the modest in vitro receptor subtype selectivity of both L-741626 (ϳ15-fold D2/D3; Grundt et al, 2007a) and PD128907 (ϳ13-fold D3/D2; Pugsley et al, 1995), it is possible that L-741626 and/or PD128907 were active at both re- ceptor subtypes at the doses tested.…”

Section: Discussionsupporting

confidence: 85%

Dopamine D3 and D2 Receptor Mechanisms in the Abuse-Related Behavioral Effects of Cocaine: Studies with Preferential Antagonists in Squirrel Monkeys

Achat-Mendes

Grundt

Cao

et al. 2010

The Journal of Pharmacology and Experimental Therapeutics

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Dopamine (DA) D3 and D2 receptor mechanisms are implicated in cocaine's abuse-related behavioral effects, but the relative contribution of the two receptor subtypes is only partially characterized. This study investigated the role of D3 and D2 subtype mechanisms by determining the degree to which the D3-preferr- were compared. In monkeys trained to discriminate cocaine from vehicle, both DA antagonists attenuated and both DA agonists partially reproduced cocaine's DS effects. PG01037 also selectively attenuated the cocaine-like DS effects of PD128907, whereas L-741626 attenuated the cocaine-like DS effects of both agonists. In self-administration studies, L-741626 nonselectively reduced cocaine-and food-maintained responding, whereas PG01037 was ineffective against either reinforcer. In studies involving reinstatement of extinguished cocaine seeking, both antagonists attenuated cocaine-induced reinstatement of responding, and both agonists induced at least partial reinstatement of cocaine seeking. L-741626 also attenuated sumanirole-induced, but not PD128907-induced, reinstatement of responding, whereas PG01037 was ineffective against either DA agonist. The results are consistent with a role for D3 and D2 receptor mechanisms in cocaine's DS effects and cocaine-induced reinstatement of drug seeking, but provide no evidence for a major role of D3 receptors in the direct reinforcing effects of cocaine.Cocaine inhibits the reuptake of DA into presynaptic terminals, resulting in stimulation of DA receptors primarily located in motor and limbic brain systems. Within the D2 family of DA receptors, there is substantial evidence for the role of the D2 receptor subtype in cocaine-induced behaviors; however, this research has not generated successful candidates for the treatment of cocaine addiction (see Xi and Gardner, 2008 for review). Considerably less is understood about the function of the D3 receptor subtype, primarily because of a lack of selective pharmacological probes that

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Section: Discussionsupporting

confidence: 85%

Dopamine D3 and D2 Receptor Mechanisms in the Abuse-Related Behavioral Effects of Cocaine: Studies with Preferential Antagonists in Squirrel Monkeys

Achat-Mendes

Grundt

Cao

et al. 2010

The Journal of Pharmacology and Experimental Therapeutics

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“…Consistent with studies that examined the discriminative stimulus effects of direct-acting dopamine receptor agonists across different feeding conditions (Appel et al 1988; Baker et al 1999; Baladi et al 2010; Bristow et al 1998; Christian et al 2001; Katz and Alling 2000; Kleven and Koek 1997; Koffarnus et al 2009; Millan et al 2000, 2007), it appears as though D3 receptors have a predominant role in mediating the discriminative stimulus effects of the indirect-acting dopamine receptor agonist cocaine in free-feeding rats whereas both D2 and D3 (and perhaps other) receptors mediate the discriminative stimulus effects of cocaine in food-restricted rats (also see Achat-Mendes et al 2010). …”

Section: Discussionsupporting

confidence: 70%

“…potency) to drugs acting at dopamine receptors (Baladi et al 2011; Collins et al 2008; Sevak et al 2008), with one study demonstrating that different dopamine receptors mediate the discriminative stimulus effects of quinpirole depending on feeding condition (Baladi et al 2010). Specifically, a number of studies have reported that the discriminative stimulus effects of nonselective D2/D3 dopamine receptor agonists, like quinpirole, are mediated by dopamine D2 receptors (Appel et al 1988; Baker et al 1999; Bristow et al 1998; Christian et al 2001; Katz and Alling 2000; Kleven and Koek 1997; Koffarnus et al 2009; Millan et al 2000, 2007). Those studies used food to maintain responding, thereby necessitating food restriction throughout the experiment.…”

Section: Introductionmentioning

confidence: 99%

Feeding condition and the relative contribution of different dopamine receptor subtypes to the discriminative stimulus effects of cocaine in rats

Baladi

Newman

2013

Psychopharmacology

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Rationale The contribution of dopamine receptor subtypes in mediating the discriminative stimulus effects of cocaine is not fully established. Many drug discrimination studies use food to maintain responding, necessitating food restriction, which can alter drug effects. Objective This study established stimulus control with cocaine (10 mg/kg) in free-feeding and food-restricted rats responding under a schedule of stimulus shock termination (SST) and in food-restricted rats responding under a schedule of food presentation to examine whether feeding condition or the reinforcer used to maintain responding impacts the effects of cocaine. Method Dopamine receptor agonists and antagonists were examined for their ability to mimic or attenuate, respectively, the effects of cocaine. Result Apomorphine, quinpirole, and lisuride occasioned >90% responding on the cocaine-associated lever in free-feeding rats responding under a schedule of SST; apomorphine, but not quinpirole or lisuride, occasioned >90% responding on the cocaine lever in food-restricted rats responding under a schedule of SST. In food-restricted rats responding for food these drugs occasioned little cocaine lever responding and were comparatively more potent in decreasing responding. In free-feeding rats, the effects of cocaine were attenuated by the D2/D3 receptor antagonist raclopride and the D3 receptor-selective antagonist PG01037. In food-restricted rats, raclopride and the D2 receptor-selective antagonist L-741,626 attenuated the effects of cocaine. Raclopride antagonized quinpirole in all groups while PG01037 antagonized quinpirole only in free-feeding rats. Conclusion These results demonstrate significant differences in the discriminative stimulus of cocaine that are due to feeding conditions and not to the use of different reinforcers across procedures.

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“…The discriminative stimulus effects of a variety of DA receptor agonists that bind to both D3 and D2 receptors are thought to be mediated by D2 receptors (Kleven and Koek, 1997;Bristow et al, 1998;Baker et al, 1999;Katz and Alling, 2000;Millan et al, 2000Millan et al, , 2007Christian et al, 2001;Koffarnus et al, 2009) based on results of studies that used DA receptor antagonists to attenuate the effects of DA receptor agonists; however, most studies used food-restricted rats. In the current study, quinpirole dose-response curves were determined in the presence of different doses of antagonists that vary in their selectivity for D3 and D2 receptors.…”

Section: Discussionmentioning

confidence: 99%

“…Collectively, studies conducted with rats suggest that the discriminative stimulus effects of a number of DA receptor agonists that bind to both D3 and D2 receptors are mediated through D2 receptors (Appel et al, 1988;Kleven and Koek, 1997;Bristow et al, 1998;Baker et al, 1999;Katz and Alling, 2000;Millan et al, 2000Millan et al, , 2007Christian et al, 2001;Koffarnus et al, 2009). For example, the discriminative stimulus effects of the D3/D2 receptor agonist S32504 are antagonized by the D2 receptorselective antagonist L-741,626 but not by the D3 receptor-selective antagonist S33084 (Millan et al, 2007), suggesting that the selective binding of S32504 to D3 receptors does not correlate with receptors mediating its discriminative stimulus effects. Moreover, the discriminative stimulus effects of the D3/D2 receptor agonist (ϩ)-PD 128,907 are antagonized by the D2 receptor-selective antagonist L-741,626 and not by the D3 receptor-selective antagonist GR 103,691 (Bristow et al, 1998).…”

mentioning

confidence: 99%

Dopamine D3 Receptors Mediate the Discriminative Stimulus Effects of Quinpirole in Free-Feeding Rats

Baladi

Newman

2010

The Journal of Pharmacology and Experimental Therapeutics

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The discriminative stimulus effects of dopamine (DA) D3/D2 receptor agonists are thought to be mediated by D2 receptors. To maintain responding, access to food is often restricted, which can alter neurochemical and behavioral effects of drugs acting on DA systems. This study established stimulus control with quinpirole in free-feeding rats and tested the ability of agonists to mimic and antagonists to attenuate the effects of quinpirole. The same antagonists were studied for their ability to attenuate quinpirole-induced yawning and hypothermia. DA receptor agonists apomorphine and lisuride, but not amphetamine and morphine, occasioned responding on the quinpirole lever. The discriminative stimulus effects of quinpirole were attenuated by the D3 receptor-selective antagonist N-{4-[4-(2,3-dichlorophenyl)-piperazin-1-yl]-trans-but-2-enyl}-4-pyridine-2-yl-benzamide HCl (PG01037) and the nonselective D3/D2 receptor antagonist raclopride, but not by the D2 receptor-selective antagonist 3-[4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl]methyl-1H-indole (L-741,626); the potencies of PG01037 and raclopride to antagonize this effect of quinpirole paralleled their potencies to antagonize the ascending limb of the quinpirole yawning dose-response curve (thought to be mediated by D3 receptors). L-741,626 selectively antagonized the descending limb of the quinpirole yawning dose-response curve, and both L-741,626 and raclopride, but not PG01037, antagonized the hypothermic effects of quinpirole (thought to be mediated by D2 receptors). Food restriction (10 g/day/7 days) significantly decreased quinpirole-induced yawning without affecting the quinpirole discrimination. Many discrimination studies on DA receptor agonists use food-restricted rats; together with those studies, the current experiment using free-feeding rats suggests that feeding conditions affecting the behavioral effects of direct-acting DA receptor agonists might also have an impact on the effects of indirect-acting agonists such as cocaine and amphetamine.Many drugs of abuse as well as many drugs used in the clinic have actions on dopamine (DA) systems; however, there are a number of different DA receptors [i.e., D1-like (D1 and D5) and D2-like (D2, D3, and D4)], and the relative contribution of each receptor subtype to the abuse or therapeutic effects of drugs is not known. For example, DA D3 and D2 receptors are thought to mediate many of the behavioral effects of cocaine because some D3/D2 receptor agonists share behavioral (e.g., discriminative stimulus) effects with cocaine (Caine and

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Discriminative stimulus properties of S32504, a novel D3/D2 receptor agonist and antiparkinson agent, in rats: attenuation by the antipsychotics, aripiprazole, bifeprunox, N-desmethylclozapine, and by selective antagonists at dopamine D2 but not D3 receptors

Abstract: The antiparkinson agent, S32504, displays DS properties principally mediated by high-efficacy activation of D(2) receptors Antipsychotics known to act as partial agonists at D(2)/D(3) receptors attenuate DS properties of S32504, actions reflecting their low efficacy at these sites.

Cited by 14 publications

References 78 publications

Dopamine D3 and D2 Receptor Mechanisms in the Abuse-Related Behavioral Effects of Cocaine: Studies with Preferential Antagonists in Squirrel Monkeys

Dopamine D3 and D2 Receptor Mechanisms in the Abuse-Related Behavioral Effects of Cocaine: Studies with Preferential Antagonists in Squirrel Monkeys

Feeding condition and the relative contribution of different dopamine receptor subtypes to the discriminative stimulus effects of cocaine in rats

Dopamine D3 Receptors Mediate the Discriminative Stimulus Effects of Quinpirole in Free-Feeding Rats

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