Chronic cocaine enhances serotonin autoregulation and serotonin uptake binding.
Repeated cocaine intoxication can result in the development of behavioral sensitization in animals and psychosis in humans, phenomena that have been associated with alterations in dopamine (DA) function. Using electrophysiologic and autoradiographic techniques, modifications of central serotonin (5-hydroxytryptamine; 5-HT) systems were investigated in rats treated with a regimen of cocaine administration that produced behavioral sensitization. The inhibitory response of single 5-HT neurons in the dorsal raphe (DR) to (-)-cocaine, the 5-HT uptake inhibitor fluoxetine or the 5-HT1A agonist 8-hydroxy-2-[di-N-propylamino]tetralin (8-OHDPAT) was significantly enhanced in cocaine-treated rats. Furthermore, several brain areas that contain either cell bodies (DR) or terminals for 5-HT (medial and sulcal prefrontal cortex, frontal cortex) showed cocaine-induced elevations in [3H]imipramine-labeled 5-HT uptake sites, while [3H]-8-OHDPAT-labeled 5-HT1A receptors were decreased only in the central medial amygdala. These results suggest that modifications of autoregulatory mechanisms secondary to alterations of 5-HT uptake processes may contribute to the development of cocaine sensitization.
Cunningham
K A
KA
Department of Pharmacology and Toxicology, University of Texas Medical School, Galveston 77550.
Paris
J M
JM
Goeders
N E
NE
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000818:Animals; D001345:Autoradiography; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000033:anatomy & histology; D001923:Brain Chemistry / Q000187:drug effects*; D003042:Cocaine / Q000494:pharmacology*; D004594:Electrophysiology; D005473:Fluoxetine / Q000494:pharmacology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism / Q000502:physiology*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology
D013764:Tetrahydronaphthalenes; D005473:Fluoxetine; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D003042:Cocaine