Biphasic alterations in serotonin-1B (5-HT1B) receptor function during abstinence from extended cocaine self-administration.
Alterations in 5-HT1B receptor function during cocaine abstinence were evaluated in rats given either limited- or extended access (LA and EA, respectively) to cocaine self-administration. The locomotor response to the 5-HT1B/1A agonist RU24969 was significantly reduced in cocaine-experienced animals relative to cocaine-naïve controls following 6 h of abstinence but became sensitized over the subsequent 14 days of abstinence. Both the early phase subsensitivity and later phase supersensivity to RU 24969-induced activity were greater in EA versus LA animals. Intra-nucleus accumbens administration of the 5-HT1B agonist CP 93, 129 produced significantly greater increases in dialysate dopamine levels in EA versus control animals following 14 days of abstinence. However, there was no difference between EA and cocaine-naïve control animals in the augmentation of cocaine-induced increases in nucleus accumbens DA produced by intra-VTA CP 93, 129. Collectively these findings demonstrate that 5-HT1B receptor function is persistently altered by cocaine self-administration.
O'Dell
Laura E
LE
Department of Psychology, The University of Texas at El Paso, El Paso, Texas, USA.
Manzardo
Ann M
AM
Polis
Ilham
I
Stouffer
David G
DG
Parsons
Loren H
LH
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D003042:Cocaine / Q000009:adverse effects*; D019970:Cocaine-Related Disorders / Q000378:metabolism* / Q000503:physiopathology; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors / Q000009:adverse effects; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D044302:Receptor, Serotonin, 5-HT1B / Q000187:drug effects* / Q000378:metabolism; D012201:Reward; D012646:Self Administration; D012701:Serotonin / Q000378:metabolism; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013375:Substance Withdrawal Syndrome / Q000378:metabolism* / Q000503:physiopathology; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000378:metabolism
D018765:Dopamine Uptake Inhibitors; D044302:Receptor, Serotonin, 5-HT1B; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D003042:Cocaine; D004298:Dopamine