Antagonism of cocaine's pharmacological effects by the stimulant dopaminergic antagonists, (+)-AJ76 and (+)-UH232

Brain Res. 1992 Aug 21;588(2):217-22. doi: 10.1016/0006-8993(92)91578-3.

Abstract

The aminotetralins (+)-AJ76 and (+)-UH232 are stimulant dopaminergic antagonists, which may preferentially antagonize autoreceptors of dopamine nerve terminals. Both agents antagonized cocaine's depressant effects on firing rates of ventral tegmental dopaminergic neurons, but (+)-UH232 was much more potent. When injected simultaneously with cocaine, (+)-UH232 inhibited and (+)-AJ76 enhanced the locomotor stimulation observed during the first 30 min following s.c. cocaine administration. However, (+)-AJ76 antagonized cocaine-induced stereotypies as well as the later more intense cocaine locomotor stimulation. It is suggested that preferential dopamine autoreceptor antagonists may provide a novel approach to a pharmacotherapy for treating cocaine abuse.

MeSH terms

  • 3,4-Dihydroxyphenylacetic Acid / metabolism
  • 8-Hydroxy-2-(di-n-propylamino)tetralin / analogs & derivatives*
  • 8-Hydroxy-2-(di-n-propylamino)tetralin / pharmacology
  • Animals
  • Behavior, Animal / drug effects*
  • Brain Chemistry / drug effects
  • Cocaine / antagonists & inhibitors*
  • Dihydroxyphenylalanine / metabolism
  • Dopamine / metabolism
  • Dopamine Antagonists*
  • Electrophysiology
  • Homovanillic Acid / metabolism
  • Male
  • Microelectrodes
  • Motor Activity / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Tetrahydronaphthalenes / pharmacology*

Substances

  • Dopamine Antagonists
  • Tetrahydronaphthalenes
  • 3,4-Dihydroxyphenylacetic Acid
  • Dihydroxyphenylalanine
  • 8-Hydroxy-2-(di-n-propylamino)tetralin
  • 5-methoxy-1-methyl-2-(n-propylamino)tetralin
  • UH 232
  • Cocaine
  • Dopamine
  • Homovanillic Acid