Antagonism of cocaine's stimulant effects on local cerebral glucose utilization by the preferential autoreceptor antagonist (+)-AJ 76.
(+)-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.
Casey
B L
BL
Upjohn Company, Kalamazoo, MI, USA.
Ray
C A
CA
Piercey
M F
MF
D000818:Animals; D001345:Autoradiography; D017660:Autoreceptors / Q000187:drug effects / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects*; D000697:Central Nervous System Stimulants / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D003042:Cocaine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D003847:Deoxyglucose; D018492:Dopamine Antagonists / Q000494:pharmacology*; D004734:Energy Metabolism / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*
D017660:Autoreceptors; D000697:Central Nervous System Stimulants; D018492:Dopamine Antagonists; D011954:Receptors, Dopamine; D013764:Tetrahydronaphthalenes; C051171:5-methoxy-1-methyl-2-(n-propylamino)tetralin; D003847:Deoxyglucose; D003042:Cocaine; D005947:Glucose