Premium
Chronic cocaine enhances serotonin autoregulation and serotonin uptake binding
Author(s) -
Cunningham Kathryn A.,
Paris Joseph M.,
Goeders Nick E.
Publication year - 1992
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.890110204
Subject(s) - serotonin , sensitization , agonist , dopamine , prefrontal cortex , raphe nuclei , 5 ht receptor , fluoxetine , pharmacology , neuroscience , methamphetamine , serotonergic , endocrinology , chemistry , medicine , psychology , receptor , cognition
Abstract 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‐HT 1A 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 [ 3 H]imipramine‐labeled 5‐HT uptake sites, while [ 3 H]‐8‐OHDPAT‐labeled 5‐HT 1A 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. © Wiley‐Liss, Inc.