Effects of hypophysectomy on compulsive checking and cortical dendrites in an animal model of obsessive-compulsive disorder.

Hormones may modulate the symptoms of obsessive-compulsive disorder (OCD), but the evidence is equivocal and not consistent across studies, with findings of hormone-associated increases and decreases of symptoms. To assess whether a strong endocrine influence on OCD exists, the effects of hypophysectomy were examined in an animal model of OCD. The model involves repeated injections of the dopamine D2/D3 receptor agonist, quinpirole, to induce locomotor sensitization and compulsive checking behavior. Intact and hypophysectomized rats were administered quinpirole (0.5 mg/kg x 6, twice weekly) or saline and compulsive checking in a large open field was measured according to a standard protocol. Results showed that in hypophysectomized animals, the development of locomotor sensitization was attenuated but the expression of quinpirole-induced compulsive checking was full-blown. Analysis of Golgi-stained neurons showed changes in spine density in Cg3 and Par1 and increased branching of apical dendrites in Cg3. It is suggested that compulsive checking could be coupled with drug-induced increases in Cg3 dendritic branching and that changes in spine density may reflect a compensatory adjustment in dopamine-innervated regions. On the basis of the animal model findings, it is concluded that the presence of OCD checking compulsions is not dependent on pituitary axis hormones.

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.