Antagonism of cocaine self-administration by the preferential dopamine autoreceptor antagonist, (+)-AJ 76.
(+)-AJ 76 is a presumed preferential dopamine (DA) autoreceptor antagonist which, in previous behavioral investigations, has displayed properties characteristic of both DA agonists and DA antagonists. In an attempt to test the hypothesis that (+)-AJ 76 might be an effective cocaine pharmacotherapy, the present experiments evaluated (+)-AJ 76's behavioral profile in 3 standard reinforcement paradigms. In the first experiment, (+)-AJ 76 paralleled a DA antagonist in that it failed to support self-administration behavior at all doses (0.1, 0.32, and 1.0 mg/kg/inj) tested. In the second experiment, (+)-AJ 76 (0.9, 3.5, and 14.0 mg/kg) closely resembled the DA agonist D-amphetamine (0.25, 1.0, and 4.0 mg/kg) in producing a clear dose-dependent conditioned place preference. In the third experiment, (+)-AJ 76 (1.88, 3.75, 7.5, 15.0, and 30.0 mg/kg) significantly reduced breaking points (BPs), increased rates of responding, and delayed the onset of responding for cocaine. While (+)-AJ 76 mimics a typical DA antagonist in its ability to reduce BPs and augment rates of responding for cocaine, recent evidence suggests that it more closely resembles a DA agonist in its ability to delay the onset of responding for cocaine. In summary, the present investigations have shown that (+)-AJ 76's profile in 3 reinforcement paradigms is unusual and not exclusively representative of either DA agonists or DA antagonists. The potential utility for such an agent in treating cocaine abuse is discussed.
Department of Psychology, Carleton University, Ottawa, Canada.
N R
NR
Richardson
M F
MF
Piercey
K
K
Svensson
R J
RJ
Collins
J E
JE
Myers
D C
DC
Roberts
D000818:Animals; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects*; D003913:Dextroamphetamine / Q000494:pharmacology; D018492:Dopamine Antagonists; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012646:Self Administration; D013237:Stereoisomerism; D019966:Substance-Related Disorders; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*
D018492:Dopamine Antagonists; D013764:Tetrahydronaphthalenes; C051171:5-methoxy-1-methyl-2-(n-propylamino)tetralin; D003042:Cocaine; D003913:Dextroamphetamine