Dopamine D1 and D2 mediation of the discriminative stimulus properties ofd-amphetamine and cocaine

Callahan, Patrick M.; Appel, James B.; Cunningham, Kathryn A.

doi:10.1007/bf02244073

Cited by 155 publications

(93 citation statements)

References 34 publications

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“…Administration of full agonists at this receptor subtype in animals trained to discriminate D-amphetamine has resulted in full substitution in some studies (Callahan et al, 1991;Nielsen et al, 1989), whereas other investigators have reported inconsistent or only partial substitution (Jarbe, 1982;Kamien and Woolverton, 1989). Consistent with their intrinsic receptor efficacy, administration of the partial D 2 agonists preclamol and SDZ 208-911 resulted in approximately 20-40% Damphetamine-appropriate responding in rats (Exner and Clark, 1992).…”

Section: Discussionmentioning

confidence: 99%

Aripiprazole Attenuates the Discriminative-Stimulus and Subject-Rated Effects of D-Amphetamine in Humans

Lile

Stoops

Vansickel

et al. 2005

Neuropsychopharmacol

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The results of animal research suggest that the use of partial agonists at dopamine (DA) D 2 receptors may be an effective strategy for the treatment of stimulant dependence. Aripiprazole is an atypical antipsychotic that has partial agonist activity at D 2 receptors. In this experiment, seven human participants with a history of nontherapeutic stimulant use learned to discriminate 15 mg oral D-amphetamine. After acquiring the discrimination (ie X80% correct responding on four consecutive sessions), the effects of a range of doses of Damphetamine (0, 2.5, 5, 10, and 15 mg), alone and in combination with aripiprazole (0 and 20 mg), were assessed. D-Amphetamine alone functioned as a discriminative stimulus, produced prototypical subject-rated drug effects (eg increased ratings of Active, Alert, Energetic) and elevated cardiovascular indices. These effects were generally a function of dose. Aripiprazole alone did not occasion D-amphetamineappropriate responding or produce subject-rated effects, but modestly impaired performance. Administration of aripiprazole significantly attenuated the discriminative-stimulus and cardiovascular effects of D-amphetamine, as well as some of the subject-rated drug effects. These data are consistent with previous preclinical findings and suggest that DA partial agonists deserve further evaluation as potential pharmacotherapies in the management of stimulant dependence. Future studies should investigate the ability of aripiprazole or related compounds to attenuate the behavioral effects of stimulants associated with a greater degree of dependence, such as methamphetamine or cocaine, in dependent individuals.

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Section: Discussionmentioning

confidence: 99%

Aripiprazole Attenuates the Discriminative-Stimulus and Subject-Rated Effects of D-Amphetamine in Humans

Lile

Stoops

Vansickel

et al. 2005

Neuropsychopharmacol

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“…Other studies clearly demonstrate that other neurochemical mechanisms contribute to the cue-effects of cocaine (e.g. Callahan et al 1991) and presumably also the reinforcing effect of cocaine (Caine and Koob 1994).…”

Section: Discussionmentioning

confidence: 99%

“…Callahan et al 1991) and presumably also the reinforcing effect of cocaine (Caine and Koob 1994). In summary, M100,907 and SB242,084 exerted different effects on cocaine-induced locomotion, cocaine-mediated reinforcement, and cocaine-induced reinstatement of responding.…”

Section: Discussionmentioning

confidence: 99%

Differential Effects of the 5-HT2A Receptor Antagonist M100,907 and the 5-HT2C Receptor Antagonist SB242,084 on Cocaine-induced Locomotor Activity, Cocaine Self-administration and Cocaine-induced Reinstatement of Responding

Fletcher

Grottick

Higgins

2002

Neuropsychopharmacology

160

254

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These studies investigated the effects of antagonists selective for the 5-HT 2A , 5-HT 2B , or 5-HT 2C receptor subtypes on behaviors elicited or maintained by cocaine. The selective 5-HT 2A receptor antagonist M100,907 (0.5 mg/kg, SC) attenuated the locomotor activity elicited by 10 mg/kg cocaine, whereas the selective 5-HT 2C receptor antagonist SB242,084 (0.5 mg/kg IP) potentiated the locomotor stimulant effect of 10 mg/kg cocaine. The selective 5-HT 2B antagonist SB215,505 (3 mg/kg PO) did not alter cocaineinduced locomotor activity. In a second series of experiments, the effects of M100,907 and SB242,084 were examined in rats self-administering cocaine intravenously according to a progressive ratio schedule. M100,907 (0.5-2 The behavioral effects of cocaine are mediated in part by increased activity of the mesolimbic dopamine (DA) system. Cocaine binds to a site on the DA transporter (McElvain and Schenk 1992) and inhibits re-uptake of released DA into presynaptic terminals. Cocaine elevates extracellular levels of DA (Di Ciano et al. 1995;Pettit and Justice 1991) and this is critical for the behavFrom the Section of Biopsychology, Centre for Addiction and Mental Health, Toronto, Ontario, Canada, and Departments of Psychiatry and Psychology, University of Toronto (PJF), and PRPN-B, Pharma Division, F. Hoffmann-La Roche Ltd., Basel, Switzerland (AJG, GAH).Address correspondence to: P.J. Fletcher, CAMH, 250 College St., Toronto, Ontario, Canada, M5T 1R8. Tel.: (416) Fax: (416) 979-6942; E-mail: Paul_Fletcher@camh.net Received October 31, 2001; revised March 12, 2002; accepted April 1, 2002. Online publication: 4/3/02 at www.acnp.org/citations/ Npp040302276. N EUROPSYCHOPHARMACOLOGY 2002 -VOL . 27 , NO . 4 5-HT 2A and 5-HT 2C Antagonists and Cocaine-mediated Behaviors 577 ioral effects of cocaine. Thus, the locomotor activating effect of cocaine is abolished in rats with 6-OHDA lesions of the mesolimbic pathway (Kelly and Iversen 1976), and similar lesions abolish self-administration of cocaine (Roberts et al. 1977;Pettit et al. 1984). DA receptor antagonists injected into the nucleus accumbens also block cocaine-induced hyperactivity (Neisewander et al. 1995), and disrupt cocaine self-administration (Maldonado et al. 1993). Although much of the work directed at understanding the neurochemical bases of the behavioral effects of cocaine has focused on DA, other neurotransmitters are likely involved. Cocaine inhibits the 5-hydroxytryptamine (5-HT, serotonin) transporter (Koe 1976) leading to enhanced levels of extracellular 5-HT (Bradberry et al. 1993), and cocaine self-administration is affected by treatments which alter 5-HT function. Increasing 5-HT availability, either by blocking re-uptake (Carroll et al. 1990;Richardson and Roberts 1991) or by administration of the 5-HT precursor L-tryptophan (McGregor et al. 1993) reduces responding for cocaine, whereas 5-HT depletion increases responding for cocaine (Loh and Roberts 1990;Roberts et al. 1994). One issue that is unresolved by previo...

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“…Pretreatment with D 1 -like antagonists, such as SCH 23390 (0.35 mg/kg) or SCH 39166 (0.1 mg/kg), reduce cocaine-appropriate responding when co-administered with cocaine, and shift the cocaine dose-effect curve to the right (Barrett and Appel 1989;Callahan et al 1991;Spealman et al 1997). Data from partial D 1 -like agonists, such as SKF 38393, and cocaine drug discrimination are inconsistent.…”

Section: Introductionmentioning

confidence: 96%

Comparison of interactions of D1-like agonists, SKF 81297, SKF 82958 and A-77636, with cocaine: locomotor activity and drug discrimination studies in rodents

Chausmer

Katz

2001

Psychopharmacology

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Rationale: Recent data suggest that dopamine (DA) D 1 -like receptor full agonists may be potential pharmacotherapeutic agents for treating cocaine abuse. The structurally novel isochroman D 1 -like agonist, A-77636, has not been well characterized and may prove to be useful as such an agent. Objectives: The interactions of cocaine and A-77636 were compared to those obtained with the better investigated benzazepine D 1 -like dopamine agonists, SKF 82958 and SKF 81297. The alterations in the locomotor stimulant and discriminativestimulus effects of cocaine by the full D 1 -like dopamine receptor agonists were investigated across a full range of doses in order to characterize their interactions. Methods: Drug-naive Swiss-Webster mice were pretreated with SKF 81297, SKF 82958 or A-77636 (1-10 mg/kg) and cocaine (5-56 mg/kg) prior to a 30-min period in which locomotor activity was assessed. Rats were trained on a fixed ratio 20 (FR20) schedule to discriminate IP saline from cocaine (10 mg/kg) injections. Cocaine alone (1-10 mg/kg) and with either A-77636 (0.56-1.7 mg/kg), SKF 82958 (0.01-0.1 mg/kg) or SKF 81297 (0.1-0.56) were injected IP 5 min prior to a 15-min test session. Results: Cocaine maximally stimulated activity at 20-40 mg/kg with higher and lower doses stimulating activity less. Each D 1 -like agonist produced a dose-related decrease in cocaine-induced locomotor activity and lowered its maximal rate. Each of the D 1 -like agonists partially substituted for cocaine, with maximal substitution approximating 49, 35, and 24% for SKF 81297, SKF 82958, and A-77636, respectively. SKF 82958 significantly shifted the cocaine dose-effect curve approximately 3-fold to the left. With SKF 81297, there was a trend towards a leftward shift of cocaine dose effects, however the change was not statistically significant. In contrast to the other two D 1 -like agonists, A-77636 either did not affect the cocaine dose-effect curve or shifted it to the right. Conclusions: All three agonists produced similar effects on cocaine-induced locomotor activity, however the discriminative-stimulus effects of cocaine were affected differently by the D 1 agonists. These results suggest fundamental differences in the actions of these D 1 agonists. Because A-77636 consistently attenuated the present effects of cocaine, it may prove more useful than the others as a pharmacotherapy to treat cocaine abuse.

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Dopamine D1 and D2 mediation of the discriminative stimulus properties ofd-amphetamine and cocaine

Cited by 155 publications

References 34 publications

Aripiprazole Attenuates the Discriminative-Stimulus and Subject-Rated Effects of D-Amphetamine in Humans

Aripiprazole Attenuates the Discriminative-Stimulus and Subject-Rated Effects of D-Amphetamine in Humans

Differential Effects of the 5-HT2A Receptor Antagonist M100,907 and the 5-HT2C Receptor Antagonist SB242,084 on Cocaine-induced Locomotor Activity, Cocaine Self-administration and Cocaine-induced Reinstatement of Responding

Comparison of interactions of D1-like agonists, SKF 81297, SKF 82958 and A-77636, with cocaine: locomotor activity and drug discrimination studies in rodents

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