Development and temporal organization of compulsive checking induced by repeated injections of the dopamine agonist quinpirole in an animal model of obsessive-compulsive disorder

Abstract

Rats treated chronically with the dopamine D2/D3 receptor agonist quinpirole develop locomotor sensitization and exhibit compulsive checking of specific places in an open-field arena, a behavioral profile that may represent an animal model of obsessive-compulsive disorder. However, it is not known how compulsive checking develops across quinpirole injections nor whether checking behavior possesses a particular temporal structure. Male rats received quinpirole (0.5mg/kg, twice weekly x 10) or an equivalent regimen of saline and were placed in a large open field for 55 min where their behavior was digitally tracked for subsequent analysis of checking behavior using existing and newly developed computer software. Results showed that the measures of compulsive checking did not follow a singular profile across injections: some remained constant and others changed monotonically reaching their near-maximum levels after about 5-7 quinpirole injections. Moreover, results showed that checking behavior was organized into bouts of checking, with the number of bouts, as well as the rate of checking within a bout, increasing across injections to reach near maximal levels after about 5-7 administrations of quinpirole. Finally, quinpirole-treated rats showed a paucity of long inter-bout intervals. These results suggest that (a) compulsive checking emerges from the operation of at least two underlying processes: a regulated process and a process of sensitization that intensifies the performance of checking behavior; and (b) quinpirole treatment may attenuate a sense of satiety that could underlie the compulsive nature of checking. Finally, because key variables measured using the newly developed algorithms showed the expected profile, the present study provides validation for the use of this methodology for the analysis of checking behavior.