Effect of nicotine on quinpirole-induced checking behavior in rats: implications for obsessive-compulsive disorder.
BACKGROUND
Rats treated chronically in a large, open field with the dopamine D2/D3 receptor agonist quinpirole (QNP) develop compulsive checking behavior as defined by a set of behavioral criteria. This paradigm has been suggested as an animal model of obsessive-compulsive disorder (OCD). Because nicotine blocks various behaviors induced by ontogenetic QNP administration, we asked whether nicotine could attenuate QNP-induced compulsive checking.


METHODS
Adult male Long-Evans rats (n = 14/group) were treated twice weekly with saline (control), or with QNP (0.5 mg/kg) for 14-16 injections. On the last two injections, rats were pretreated in random order with an acute dose of nicotine (0.3 mg/kg base) or saline 10 min before administration of QNP or saline; and the effects on checking behavior was examined. The effects of chronic QNP treatment on nicotinic receptors in discrete brain regions were also determined.


RESULTS
Chronic QNP resulted in compulsive checking and increases in cerebellar alpha4beta2 and alpha7 nicotinic receptor densities. Nicotine pretreatment significantly reduced one of the three measures of compulsive checking behavior.


CONCLUSIONS
Nicotine attenuates some symptoms of compulsive checking in a rat model of OCD; however, the mechanisms of this effect and therapeutic efficacy of nicotinic agonists in OCD require further study.
Tizabi
Yousef
Y
Department of Pharmacology, College of Medicine, Howard University, Washington, DC 20059, USA.
Louis
Vely A
VA
Taylor
Charles T
CT
Waxman
Donna
D
Culver
Kirsten E
KE
Szechtman
Henry
H
D000818:Animals; D001921:Brain / Q000187:drug effects; D004195:Disease Models, Animal; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009538:Nicotine / Q000494:pharmacology*; D009771:Obsessive-Compulsive Disorder / Q000139:chemically induced* / Q000523:psychology; D019257:Quinpirole / Q000037:antagonists & inhibitors / Q000633:toxicity*; D051381:Rats; D020318:Rats, Long-Evans; D011978:Receptors, Nicotinic / Q000187:drug effects; D013239:Stereotyped Behavior / Q000187:drug effects*
D011978:Receptors, Nicotinic; D019257:Quinpirole; D009538:Nicotine