title: Isolation rearing impairs the reinforcing efficacy of intravenous cocaine or intra-accumbens d-amphetamine: impaired response to intra-accumbens D1 and D2/D3 dopamine receptor antagonists.
abstract: Male Lister hooded rats were raised from weaning either alone (isolation reared) or in groups of five (socially reared controls). At 5 months of age, bilateral guide cannulae were implanted within the nucleus accumbens, and experiments began. The effect of isolation rearing upon the reinforcing efficacy of the intravenous self-administration of cocaine (experiment 1), or the bilateral intra-accumbens self-administration of d-amphetamine (experiment 2) was assessed. Self-administration was made contingent upon the acquisition of a novel lever-pressing response. Two identical levers were available within each operant chamber. Responding on one lever resulted in the delivery of drug (experiment 1: cocaine, 1.5 mg/kg per infusion; experiment 2: d-amphetamine, 0.25 micrograms/side), responding on the second, control lever was recorded but had no programmed consequences. Animals were not "primed" with noncontingent infusions at any time. For experiment 1, animals received intra-accumbens infusions of the D1 dopamine receptor antagonist SCH-23390, or the D2 dopamine receptor antagonist sulpiride over two test sessions. Within each session, animals received a cumulative series of doses of each dopamine receptor antagonist. A validation group received doses of each antagonist according to more conventional methods (one dose per session). In either case, intra-accumbens infusions of SCH-23390 or sulpiride enhanced the rate of the self-administration of cocaine in socially reared controls. However, isolation rearing impaired this response to intra-accumbens infusions of the dopamine receptor antagonists. Experiment 2a examined the acquisition of the intra-accumbens self-administration of d-amphetamine. Socially reared controls acquired readily a selective response upon the drug lever. However, isolation reared animals acquired a selective response at a greatly retarded rate. In experiment 2b, a full d-amphetamine dose-response function was examined. Isolation rearing impaired the response to a range of doses of d-amphetamine. In experiment 2c, the infusate (1 microgram d-amphetamine per infusion) was adulterated with either SCH-23390 or sulpiride. Adulteration with either dopamine receptor antagonist enhanced the rate of response by socially reared controls. Isolation rearing impaired this response to SCH-23390, and blocked the response to sulpiride. These data are discussed in relation to the functioning of cortico-limbic-striatal systems, with particular reference to the mesoaccumbens dopamine projection.
authors.affiliation: Department of Experimental Psychology, University of Cambridge, UK.
authors.forename: G D
authors.initials: GD
authors.lastname: Phillips
authors.forename: S R
authors.initials: SR
authors.lastname: Howes
authors.forename: R B
authors.initials: RB
authors.lastname: Whitelaw
authors.forename: T W
authors.initials: TW
authors.lastname: Robbins
authors.forename: B J
authors.initials: BJ
authors.lastname: Everitt
mesh_terms: D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects; D003913:Dextroamphetamine / Q000008:administration & dosage / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D065127:Dopamine D2 Receptor Antagonists; D004305:Dose-Response Relationship, Drug; D007267:Injections; D007275:Injections, Intravenous; D008297:Male; D009714:Nucleus Accumbens / Q000502:physiology*; D051381:Rats; D011954:Receptors, Dopamine / Q000187:drug effects; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors; D050637:Receptors, Dopamine D3; D012054:Reinforcement, Psychology; D012646:Self Administration; D012934:Social Isolation; D013469:Sulpiride / Q000494:pharmacology
chemical_list: D001552:Benzazepines; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; C493595:Drd3 protein, rat; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D050637:Receptors, Dopamine D3; D013469:Sulpiride; D003042:Cocaine; D003913:Dextroamphetamine