Stimulation of 5-HT1B receptors decreases cocaine- and sucrose-seeking behavior.
Serotonin systems have been implicated in incentive motivation for cocaine, yet little is known about the role of 5-HT(1B) receptors in these processes. We used the extinction/reinstatement model to examine the effects of the 5-HT(1B/1A) receptor agonist, RU24969, on reinstatement of extinguished cocaine-seeking behavior. Rats trained to self-administer cocaine subsequently underwent extinction. They were then tested twice for cue and cocaine-primed reinstatement of extinguished cocaine-seeking behavior, receiving saline pretreatment 1 day and their assigned dose of RU24969 (0.3, 1.0, 3.0 mg/kg) the other day. Rats were later trained on a schedule of sucrose reinforcement in novel chambers and then tested for effects of RU24969 on cue reinstatement of sucrose-seeking behavior and locomotion. RU24969 decreased cue and cocaine reinstatement of cocaine-seeking behavior and cue reinstatement of sucrose-seeking behavior. Locomotion was increased only at the highest RU24969 dose (3 mg/kg). A subsequent experiment demonstrated that the effects of RU24969 (1 mg/kg) on extinguished cocaine-seeking behavior were reversed by the 5-HT(1B) antagonist GR127935 (3 mg/kg). These findings suggest that the effects of RU24969 on cue and cocaine reinstatement of cocaine-seeking behavior are 5-HT(1B) receptor-mediated. Overall, the results suggest that stimulation of 5-HT(1B) receptors may produce a general decrease in motivation.
Acosta
Jazmin I
JI
Department of Psychology, Arizona State University, Box 871104 Tempe, AZ 85287-1104, USA.
Boynton
Floren A
FA
Kirschner
Kenneth F
KF
Neisewander
Janet L
JL
D000818:Animals; D016739:Behavior, Addictive / Q000378:metabolism*; D003042:Cocaine / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D005247:Feeding Behavior / Q000187:drug effects / Q000502:physiology*; D007211:Indoles / Q000494:pharmacology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D044302:Receptor, Serotonin, 5-HT1B / Q000378:metabolism* / Q000502:physiology; D058825:Serotonin 5-HT1 Receptor Agonists; D013395:Sucrose / Q000008:administration & dosage*
D007211:Indoles; D044302:Receptor, Serotonin, 5-HT1B; D058825:Serotonin 5-HT1 Receptor Agonists; C025145:5-methoxy 3-(1,2,3,6-tetrahydro-4-pyridinyl)1H indole; D013395:Sucrose; D003042:Cocaine