Serotonin1b receptor stimulation enhances dopamine-mediated reinforcement.
The effect of 5-HT1B receptor stimulation on dopamine-mediated reinforcement in rats was investigated using intravenous self-administration of the selective dopamine uptake inhibitor GBR-12909 on an FR5 schedule of reinforcement. Pretreatment with the 5-HT1A/1B receptor agonist CGS-12066B (1-10 mg/kg, IP) dose-dependently reduced the self-administration of GBR-12909 (83 micrograms/injection) by increasing the interval between drug injections, consistent with a enhancement of the reinforcing effects of GBR-12909. Additionally, CGS-12066B pretreatment (3 mg/kg, IP) shifted the dose-effect function for GBR-12909 self-administration to the left. Pretreatment with the selective 5-HT1A receptor agonist 8-OH-DPAT (0.03-1.0 mg/kg, SC) had no significant effect on GBR-12909 self-administration (83 micrograms/injection), indicating that the effect of CGS-12066B is not mediated by the 5-HT1A receptor. Finally, CGS-12066B pretreatment (1-10 mg/kg, IP) did not alter the self-administration of cocaine (0.03-0.5 mg/injection), suggesting that the simultaneous stimulation of multiple 5-HT receptor subtypes by the indirect 5-HT agonist properties of cocaine may mask the effect of 5-HT1B receptor stimulation on DA-mediated reinforcement.
Parsons
L H
LH
Department of Neuropharmacology, Scripps Research Institute, La Jolla, CA 92037, USA.
Weiss
F
F
Koob
G F
GF
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D003042:Cocaine / Q000008:administration & dosage; D003216:Conditioning, Operant / Q000187:drug effects*; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D009294:Narcotics / Q000008:administration & dosage; D010879:Piperazines / Q000008:administration & dosage*; D011810:Quinoxalines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D044302:Receptor, Serotonin, 5-HT1B; D011985:Receptors, Serotonin / Q000187:drug effects*; D012646:Self Administration; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
D018765:Dopamine Uptake Inhibitors; D009294:Narcotics; D010879:Piperazines; D011810:Quinoxalines; D044302:Receptor, Serotonin, 5-HT1B; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; C052561:CGS 12066B; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C043425:vanoxerine; D003042:Cocaine