Chronic cocaine treatment impairs the regulation of synaptosomal 3H-DA release by D2 autoreceptors.
The effect of repeated administration of cocaine on presynaptic D2 autoreceptor sensitivity in synaptosomes was studied. In rats treated chronically with saline, the dopamine D2 agonist 2-(N-propyl-N-2-thienylethylamino)-5-hydroxytetralin (N-0437) caused a significant inhibition of the Ca2(+)-evoked 3H-DA release from synaptosomes prepared from the nucleus accumbens and from the striatum; this effect was blocked by the D2 antagonist sulpiride. However, chronic cocaine pretreatment abolished the effect of N-0437 in both areas, suggesting a subsensitivity of release-modulating terminal DA autoreceptors. Subsensitive DA autoreceptors would enhance stimulated DA release from mesolimbic and nigrostriatal terminals and may play a role in the behavioral sensitization observed in this paradigm.
Yi
S J
SJ
Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston 77550.
Johnson
K M
KM
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002118:Calcium / Q000494:pharmacology; D003042:Cocaine / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology; D005260:Female; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism*; D017448:Receptors, Dopamine D2; D013469:Sulpiride / Q000494:pharmacology; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D013876:Thiophenes / Q000494:pharmacology
D015259:Dopamine Agents; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D013764:Tetrahydronaphthalenes; D013876:Thiophenes; D013469:Sulpiride; C047508:rotigotine; D003042:Cocaine; D002118:Calcium; D004298:Dopamine