5-HT(1B) receptors in nucleus accumbens efferents enhance both rewarding and aversive effects of cocaine.
Whether serotonin-1B (5-HT(1B)) receptor activation enhances or diminishes the reinforcing properties of psychostimulants remains unclear. We have previously shown that increased expression of 5-HT(1B) receptors in nucleus accumbens (NAcc) shell neurons sensitized rats to the locomotor-stimulating and rewarding properties of cocaine. In this study we further examined the contribution of 5-HT(1B) receptors on the effect of cocaine under conditions intended to selectively influence either conditioned place preference or avoidance (CPP or CPA, respectively). Viral-mediated gene transfer techniques were used to overexpress 5-HT(1B) receptors in medial NAcc shell medium spiny neurons projecting to the ventral tegmental area. Animals were then conditioned to associate place cues with the effects of either a low (5 mg/kg) or moderately high (20 mg/kg) dosage of cocaine immediately or 45 min after intraperitoneal cocaine administration. Animals with increased 5-HT(1B) expression showed cocaine-induced CPP immediately after administration of the low 5 mg/kg dose of cocaine, but a CPA 45 min after administration of the high 20 mg/kg dose. Control animals showed no preference at the 5 mg/kg dose and a significant preference at 20 mg/kg. Given this, we believe that increased 5-HT(1B) receptor activation in NAcc shell projection neurons intensifies both the rewarding and negative properties of cocaine use.
Barot
Sabiha K
SK
Program of Neurobiology and Behavior, Department of Psychology, Box 351525, University of Washington, Seattle, WA 98195, USA.
Ferguson
Susan M
SM
Neumaier
John F
JF
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology; D003042:Cocaine / Q000009:adverse effects*; D019970:Cocaine-Related Disorders / Q000378:metabolism* / Q000503:physiopathology; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology; D018765:Dopamine Uptake Inhibitors / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D005822:Genetic Vectors; D007274:Injections, Intraperitoneal; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044302:Receptor, Serotonin, 5-HT1B / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D012201:Reward; D012701:Serotonin / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D014162:Transfection
D018765:Dopamine Uptake Inhibitors; D044302:Receptor, Serotonin, 5-HT1B; D012701:Serotonin; D003042:Cocaine