title: Effects of dopamine D(2)-like receptor agonists in mice trained to discriminate cocaine from saline: influence of feeding condition.
abstract: In rats, the discriminative stimulus effects of direct- and indirect-acting dopamine receptor agonists are mediated by multiple dopamine receptor subtypes and the relative contribution of dopamine D2 and D3 receptors to these effects varies as a function of feeding condition. In these studies, free-fed and food-restricted mice were trained to discriminate 10.0mg/kg cocaine using a two-lever discrimination procedure in which responding was maintained by food. Both groups of mice acquired the discrimination; however, free-fed mice responded at lower rates than food-restricted mice. Dopamine D3 receptor agonists, pramipexole and quinpirole, increased cocaine-appropriate responding (>85%) in food-restricted, but not in free-fed mice. The dopamine D2 receptor agonist, sumanirole, and the nonselective dopamine receptor agonist, apomorphine, failed to increase cocaine-appropriate responding in either group. Free-fed mice were more sensitive than food-restricted mice to the rate-decreasing effects of dopamine receptor agonists and these effects could not be overcome by increasing the magnitude of reinforcement. Because feeding condition did not alter quinpirole-induced hypothermia, it is unlikely that differences in the discriminative stimulus or rate-decreasing effects of dopamine D2-like receptor agonists were due to differences in the pharmacokinetic properties of the drugs. Although these results suggest that the discriminative stimulus effects of cocaine are mediated by both dopamine D2 and D3 receptors in food-restricted mice, the increased sensitivity of free-fed mice to the rate-decreasing effects of dopamine D2-like receptor agonists limited conclusions about the impact of feeding conditions on the relative contribution of dopamine D2 and D3 receptors to the discriminative stimulus effects of cocaine.
authors.affiliation: Department of Pharmacology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr., Mail Code 7764, San Antonio, TX 78229, USA. Electronic address: collinsg@uthscsa.edu.
authors.forename: Gregory T
authors.initials: GT
authors.lastname: Collins
authors.affiliation: Department of Pharmacology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr., Mail Code 7764, San Antonio, TX 78229, USA.
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Jackson
authors.affiliation: Department of Pharmacology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr., Mail Code 7764, San Antonio, TX 78229, USA; Department of Psychiatry, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr., Mail Code 7764, San Antonio, TX 78229, USA.
authors.forename: Wouter
authors.initials: W
authors.lastname: Koek
authors.affiliation: Department of Pharmacology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr., Mail Code 7764, San Antonio, TX 78229, USA; Department of Psychiatry, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr., Mail Code 7764, San Antonio, TX 78229, USA.
authors.forename: Charles P
authors.initials: CP
authors.lastname: France
mesh_terms: D000818:Animals; D003042:Cocaine / Q000008:administration & dosage*; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology; D004193:Discrimination Learning / Q000187:drug effects / Q000502:physiology*; D018491:Dopamine Agonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005247:Feeding Behavior / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017448:Receptors, Dopamine D2 / Q000819:agonists* / Q000502:physiology; D012965:Sodium Chloride / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D018491:Dopamine Agonists; D017448:Receptors, Dopamine D2; D012965:Sodium Chloride; D003042:Cocaine
keywords: (−)-Cocaine HCl (PubChem CID: 656832); (−)-Quinpirole HCl (PubChem CID: 55397); Apomorphine HCl (PubChem CID: 9410); Cocaine; Dopamine D(2) receptors; Dopamine D(3) receptors; Drug discrimination; Food-restriction; Free-feeding; Mice; Pramipexole dihydrochloride (PubChem CID: 119569); Sumanirole maleate (PubChem CID: 9818478); d-amphetamine sulfate (PubChem CID: 5825)