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

Abstract

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.