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.
Richardson
N R
NR
Department of Psychology, Carleton University, Ottawa, Canada.
Piercey
M F
MF
Svensson
K
K
Collins
R J
RJ
Myers
J E
JE
Roberts
D C
DC
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