Antagonism of cocaine's stimulant effects on local cerebral glucose utilization by the preferential autoreceptor antagonist (+)-AJ 76.

Abstract

(+)-AJ 76 is a stimulant dopamine (DA) antagonist, which has a putative preferential action at DA nerve terminal autoreceptors. Because it is both a mild stimulant and a DA antagonist, it has previously been suggested that (+)-AJ 76 might antagonize both the euphoria and craving associated with cocaine abuse and withdrawal, respectively. To evaluate this hypothesis further, (+)-AJ 76 was evaluated for its ability to affect cocaine-induced changes in regional brain energy metabolism. Using Sokoloff's 2-deoxyglucose autoradiographic technique, (+)-AJ 76 antagonized the stimulant effect of cocaine. Although classical DA antagonists are known to depress regional brain energy metabolism, (+)-AJ 76 by itself had no effect. It is concluded that the results are consistent with the previously stated hypothesis that (+)-AJ 76 might be useful as a pharmacotherapy for treatment of cocaine abuse.

• Authors: B L Casey, C A Ray, M F Piercey
• Journal: Journal of neural transmission (Vienna, Austria : 1996) (J Neural Transm (Vienna)) Vol. 103 Issue 3 Pg. 277-85 ( 1996) ISSN: 0300-9564 [Print] Austria
• PMID: 8739839 (Publication Type: Journal Article)

Chemical References

• Autoreceptors
• Central Nervous System Stimulants
• Dopamine Antagonists
• Receptors, Dopamine
• Tetrahydronaphthalenes
• 5-methoxy-1-methyl-2-(n-propylamino)tetralin
• Deoxyglucose
• Cocaine
• Glucose

Topics

• Animals
• Autoradiography
• Autoreceptors (drug effects, metabolism)
• Brain Chemistry (drug effects)
• Central Nervous System Stimulants (antagonists & inhibitors, pharmacology)
• Cocaine (antagonists & inhibitors, pharmacology)
• Deoxyglucose
• Dopamine Antagonists (pharmacology)
• Energy Metabolism (drug effects)
• Glucose (metabolism)
• Male
• Rats
• Rats, Sprague-Dawley
• Receptors, Dopamine (drug effects, metabolism)
• Tetrahydronaphthalenes (pharmacology)