Assessment of cocaine-like discriminative stimulus effects of dopamine D3 receptor ligands

Acri, Jane B.; Carter, Sean R.; Alling, Ken; Geter-Douglass, Beth; Dijkstra, Durk; Wikström, Håkan; Katz, Jonathan L.; Witkin, Jeffrey M.

doi:10.1016/0014-2999(95)00411-d

Cited by 66 publications

(56 citation statements)

References 5 publications

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“…Furthermore, D 3 receptor overexpression has been proposed to be responsible for the sensitization to DA agonists. Consistent with these observations, a growing body of evidence also involves the D 3 receptor in mechanisms of drug dependence and abuse: (1) DA D 3 receptors are implicated in cue-controlled modulation of cocaine seeking behavior (Pilla et al, 1999;Di Ciano et al, 2001;Vorel et al, 2002) and cocaine cue-conditioned hyperactivity (Le Foll et al, 2002); (2) DA D 3 receptorpreferring agonists generalize from the discriminative stimulus effects of cocaine (Acri et al, 1995); (3) DA D 3 receptor-preferring agonists can be self-administered (Caine et al, 1997;Caine and Koob, 1993), and (4) DA D 3 receptor-preferring agonists can produce conditioned place preference (Khroyan et al, 1997). Altogether these findings suggest an important role of DA D 3 receptors in the mechanisms by which atypical APDs enhance DA, NE, and ACh in the mPFC.…”

Section: Discussionmentioning

confidence: 88%

Selective Antagonism at Dopamine D3 Receptors Enhances Monoaminergic and Cholinergic Neurotransmission in the Rat Anterior Cingulate Cortex

Lacroix

Hows

Shah

et al. 2002

Neuropsychopharmacol

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Recent neuroanatomical and functional investigations focusing on dopamine (DA) D 3 receptors have suggested a potential role of this receptor in psychiatric diseases such as schizophrenia and drug dependence. In line with the key role of the prefrontal cortex in psychiatric disorders, the present study aimed at assessing the effects of the acute systemic administration of the selective DA D 3 receptor antagonist SB-277011-A on the in vivo extracellular levels of monoamines (DA, norepinephrine (NE), and serotonin (5-HT)) and acetylcholine (ACh) in the anterior cingulate subregion of the medial prefrontal cortex. The in vivo neurochemical profile of SB-277011-A (10 mg/kg, i.p.) in the anterior cingulate cortex was compared with both typical and atypical antipsychotics including clozapine (10 mg/kg, s.c.), olanzapine (10 mg/kg, s.c.), sulpiride (10 mg/kg, s.c.), and haloperidol (0.5 mg/kg, s.c.). The acute administration of SB-277011-A, clozapine, and olanzapine produced a significant increase in extracellular levels of DA, NE, and ACh without affecting levels of 5-HT. Sulpiride also significantly increased extracellular DA, but with a delayed onset over SB-277011-A, clozapine, and olanzapine. In contrast, haloperidol failed to alter any of the three monoamines and ACh in the anterior cingulate cortex. These findings add to a growing body of evidence suggesting a differentiation between typical and atypical antipsychotic drugs (APDs) in the anterior cingulate cortex and a role of DA D 3 receptors in desired antipsychotic drug profile. Similar to their effects on DA and NE, SB-277011-A, clozapine, and olanzapine increased extracellular levels of ACh, whereas haloperidol and sulpiride did not alter ACh. The results obtained in the present study provide evidence of the important role of DA D 3 receptors in the effect of pharmacotherapeutic agents that are used for the treatment of psychiatric disorders such as schizophrenia and drug dependence.

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Section: Discussionmentioning

confidence: 88%

Selective Antagonism at Dopamine D3 Receptors Enhances Monoaminergic and Cholinergic Neurotransmission in the Rat Anterior Cingulate Cortex

Lacroix

Hows

Shah

et al. 2002

Neuropsychopharmacol

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“…For instance, in rats trained to self-administer cocaine, D 3 Rpreferring agonists quinelorane,PD 128,907) enhanced the reinforcing efficacy of this drug and D 3 Rpreferring antagonists (l-nafadotride, (+)-AJ 76, (+)-UH 232) had the opposite effect Koob, 1993, 1995;Richardson et al, 1993;Smith et al, 1995;Parsons et al, 1996;Caine et al, 1997Caine et al, , 1999, although a more selective D 3 R antagonist, SB-277011-A, was inactive in this respect (Di Ciano et al, 2003). The D 3 R-preferring agonists were selfadministered (Caine and Koob, 1993;Parsons et al, 1996); they induced conditioned place preference (CPP) (Mallet and Beninger, 1994;Chaperon and Thiébot, 1996;Khroyan et al, 1997; but see Khroyan et al, 1995;Rodríguez de Fonseca et al, 1995), and/or they generalized from the damphetamine or the cocaine stimulus effects in drugdiscrimination tasks (Acri et al, 1995;Bevins et al, 1997;Baker et al, 1998;Garner and Baker, 1999), indicating that the stimulation of D 3 R may exert reinforcing effects and induce some of the subjective effects of psychostimulants.…”

Section: Introductionmentioning

confidence: 99%

Effects of a Dopamine D3 Receptor Ligand, BP 897, on Acquisition and Expression of Food-, Morphine-, and Cocaine-induced Conditioned Place Preference, and Food-seeking Behavior in Rats

Duarte

Lefebvre

Chaperon

et al. 2003

Neuropsychopharmacol

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The present study addressed the role of dopaminergic D 3 receptors (D 3 R) in motivational processes in rats. The effects of the selective D 3 R partial agonist, BP 897 (0.25-1 mg/kg, i.p.), on the establishment and the expression of conditioned place preference (CPP) supported by food, morphine (4 mg/kg, s.c.), or cocaine (2 mg/kg, s.c.) were investigated using an unbiased, one-compartment, placeconditioning procedure. When administered alone, BP 897 (0.05-2 mg/kg, i.p.) did not support CPP; on the contrary, conditioned place avoidance (CPA) was observed at 1 mg/kg, suggesting that this dose of BP 897 could be perceived as aversive. When given before each cocaine injection during the conditioning phase, BP 897 (1 mg/kg) prevented the establishment of CPP, and a single administration of BP 897 (0.5 and 1 mg/kg) before the test session impaired the expression of cocaine CPP. In contrast, neither the establishment nor the expression of food-and morphine-CPP were significantly altered by BP 897 (up to 1 mg/kg), whereas the full but less selective D 3 /D 2 R agonists, 7-OH-DPAT (0.5-2 mg/kg, s.c.) and quinelorane (1 mg/kg, s.c.), prevented the acquisition of food CPP. In a within-session extinction schedule of lever pressing for food, BP 897 (0.06-2 mg/kg) was ineffective in potentiating response reinstatement induced by the noncontingent delivery of two food pellets, in contrast with quinelorane and 7-OH-DPAT where previous studies showed to be efficient in this respect (Duarte et al, 2003). These results indicate that BP 897 has no positive appetitive value on its own, and that a moderate degree of stimulation of D 3 R is not sufficient to modulate food-primed food-seeking behavior or alter incentive motivation for food, morphine, and/or their associated cues. However, D 3 R are likely involved in the perception of the rewarding value of cocaine and cocaine-paired cues. This suggests that the appetitive effects of cocaine are subserved by mechanisms different, at least in part, from those of morphine and food, and that D 3 R play a role only in the former.

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“…Recently, it has been shown that antagonism of D3 receptors in the NAc shell using the D3-preferential antagonist nafadotride increased levels of impulsivity in highly impulsive rats, whereas antagonism in the NAc core had the opposite effect (Besson et al, 2010). Finally, it has been suggested that D3 mechanisms play an integral role in the transduction of cocaine's discriminative stimulus (DS) effects based on findings by Acri et al (1995) and Spealman (1996) in which drugs acting as preferential agonists at D3 receptors, such as PD128907 [R-(ϩ)-trans-3,4a,10b-tetrahydro-4-propyl-2H,5H-[1]benzopyrano [4,3-b]-1,4-oxazin-9-ol)] and 7-OH-DPAT [7-hydroxy-N,N-dipropyl-2-aminotetralin], partially reproduced cocaine's DS effects in rats and monkeys. Conversely, blocking D3 activity with D3-preferring antagonists or partial agonists, such as NGB2904 [N-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butyl)-9H-fluorene-2-carboxamide] and CJB090 [N-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butyl)-4-(pyridin-2-yl)benzamidehave] has been shown in some cases to attenuate the DS, priming or reinforcing effects of cocaine (Xi et al, 2006;Martelle et al, 2007;Achat-Mendes et al, 2009).…”

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confidence: 99%

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

J Pharmacol Exp Ther

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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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Assessment of cocaine-like discriminative stimulus effects of dopamine D3 receptor ligands

Cited by 66 publications

References 5 publications

Selective Antagonism at Dopamine D3 Receptors Enhances Monoaminergic and Cholinergic Neurotransmission in the Rat Anterior Cingulate Cortex

Selective Antagonism at Dopamine D3 Receptors Enhances Monoaminergic and Cholinergic Neurotransmission in the Rat Anterior Cingulate Cortex

Effects of a Dopamine D3 Receptor Ligand, BP 897, on Acquisition and Expression of Food-, Morphine-, and Cocaine-induced Conditioned Place Preference, and Food-seeking Behavior in Rats

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

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