Stimulation of 5-HT2C receptors attenuates cue and cocaine-primed reinstatement of cocaine-seeking behavior in rats.
The extinction/reinstatement model has been used in this study to examine the role of 5-HT2C receptors in cocaine-seeking behavior elicited by cocaine-associated cues and cocaine-priming injections. Rats that had been trained to press a lever for cocaine (0.75 mg/kg/0.1 ml, intravenously) paired with light and tone cues underwent daily extinction sessions, during which responding had no consequences. After responding diminished, rats were tested for reinstatement of responding by either response-contingent presentations of the cues or a cocaine-priming injection (10 mg/kg, intraperitoneal, i.p.), with and without pretreatment with the 5-HT2C/2B receptor agonist, MK 212 (0.0-1.0 mg/kg, i.p.). MK 212 attenuated cue and cocaine-primed reinstatement, as well as spontaneous and cocaine-induced locomotion at all doses tested. These effects were reversed by coadministration of the 5-HT2C-selective receptor antagonist, SB 242 084 (3.0 mg/kg, i.p.), suggesting they are 5-HT2C receptor-mediated. Although we cannot rule out the possibility that motor impairment might have been involved in the MK 212 effects on cocaine-seeking behavior, some aspects of the data favor the explanation that MK 212 decreases the motivational effects of cocaine and cocaine cues. The latter interpretation is consistent with a growing body of literature suggesting that 5-HT2C receptors play a role in motivated behaviors in general.
Neisewander
Janet L
JL
Department of Psychology, Arizona State University, Tempe, Arizona 85287-1104, USA. janet.neisewander@asu.edu
Acosta
Jazmin I
JI
D000631:Aminopyridines / Q000494:pharmacology; D000818:Animals; D016739:Behavior, Addictive / Q000503:physiopathology*; D003042:Cocaine / Q000008:administration & dosage*; D003463:Cues; D004305:Dose-Response Relationship, Drug; D005108:Extinction, Psychological / Q000187:drug effects*; D007211:Indoles / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D011719:Pyrazines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044405:Receptor, Serotonin, 5-HT2C / Q000502:physiology*; D012646:Self Administration
C107820:6-chloro-5-methyl-1-((2-(2-methylpyrid-3-yloxy)pyrid-5-yl)carbamoyl)indoline; D000631:Aminopyridines; D007211:Indoles; D011719:Pyrazines; D044405:Receptor, Serotonin, 5-HT2C; C014896:6-chloro-2-(1-piperazinyl)pyrazine; D003042:Cocaine