Variations in cocaine self-administration by inbred rat strains under a progressive-ratio schedule.
This study investigated the influence of genetics on extent of cocaine taking in rats that were self-administering cocaine under a progressive-ratio schedule. Fischer 344, ACI and Brown Norway rats were subjects because previous genetic studies on dopamine receptor loci have indicated that these are genetically divergent strains. All subjects were assessed for acquisition and stability of cocaine self-administration under a progressive ratio schedule. Subsequently, a dose-effect curve for cocaine self-administration was determined for each strain. Fischer 344 rats maintained a higher average breaking point than did the ACI or Brown Norway strains. In addition, dopamine receptor antagonists differentially reduced the ability of cocaine to serve as a reinforcer across the three strains. The D1-selective dopamine receptor antagonist, SCH 23390, and the D2/D3-selective dopamine receptor antagonist, eticlopride were significantly more effective in reducing the self-administration of cocaine in Brown Norway rats than for the other two strains. The results of this study demonstrate that genetic differences may play an important role in determining responding under progressive-ratio schedules for cocaine, possibly due to differences in the reinforcing efficacy of cocaine.
Division on Substance Abuse York State Psychiatric Institute, New York, NY, USA.
A S
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Ward
D H
DH
Li
R R
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Luedtke
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MW
Emmett-Oglesby
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001552:Benzazepines / Q000494:pharmacology; D003042:Cocaine / Q000008:administration & dosage*; D003216:Conditioning, Operant / Q000187:drug effects; D018492:Dopamine Antagonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D009294:Narcotics / Q000008:administration & dosage*; D051381:Rats; D011914:Rats, Inbred BN; D011916:Rats, Inbred F344; D012457:Salicylamides / Q000494:pharmacology; D012646:Self Administration
D001552:Benzazepines; D018492:Dopamine Antagonists; D009294:Narcotics; D012457:Salicylamides; D003042:Cocaine; C045989:eticlopride