Chronic cocaine treatment impairs the regulation of synaptosomal 3H-DA release by D2 autoreceptors

• Published in: Pharmacology, biochemistry and behavior Vol. 36; no. 3; pp. 457 - 461
• Main Authors: SU-JIN YI, JOHNSON, K. M
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Science 01.07.1990
• Subjects: Animals; Behavior, Animal - drug effects; Biological and medical sciences; Calcium - pharmacology; Cocaine - pharmacology; Corpus Striatum - drug effects; Corpus Striatum - metabolism; Dopamine - metabolism; Dopamine Agents - pharmacology; Female; Medical sciences; Neuropharmacology; Nucleus Accumbens - drug effects; Nucleus Accumbens - metabolism; Pharmacology. Drug treatments; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Rats; Rats, Inbred Strains; Receptors, Dopamine - drug effects; Receptors, Dopamine - metabolism; Receptors, Dopamine D2; Sulpiride - pharmacology; Synaptosomes - drug effects; Synaptosomes - metabolism; Tetrahydronaphthalenes - pharmacology; Thiophenes - pharmacology; Brain; Intraperitoneal administration; Rat; Psychotropic; Central nervous system; Multiple dose; Regulation(control); Synaptosome; Hallucinogen; Drug of abuse; Behavior; Release; Dopamine; CNS stimulant; Rodentia; Autoreceptor; Corpus striatum; Nucleus accumbens; Vertebrata; Chronic; Sensitivity; Mammalia; D2 Dopamine receptor; Animal; Cocaine
• ISSN: 0091-3057; 1873-5177
• DOI: 10.1016/0091-3057(90)90241-9

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.