EFFECTS OF THE NOVEL ATYPICAL ANTIPSYCHOTIC, ARIPIPRAZOLE, ON RATS PERFORMING SIGNALED AND UNSIGNALED TEMPORAL DISCRIMINATION TASKS.

In contrast to other atypical antipsychotics, aripiprazole (ARZ) acts as a partial agonist, rather than an antagonist, at dopamine D2 receptors (Burris et al, 2002; Jordan et al, 2002). This unique pharmacology is thought to be essential to its multi-faceted use in the treatment of other disorders, particularly in its use as an adjunctive treatment for Major Depressive Disorder (Biler & Blondeau, 2011). Currently, little treatment is available to attenuate cognitive dysfunction in schizophrenic individuals (Schatzberg et al, 2010). However, clinical and neurocognitive studies have reported ARZ to improve cognition in schizophrenic subjects (Leuchet et al, 2003; Schatzberg et al, 2010), as well as attenuate working memory impairments and attentional deficits in animal models of psychosis (Carli et al, 2010; Nordquest et al, 2008; Nagi et a, 2008). Further evaluation of ARZ is needed to assess its ability to ameliorate higher-order cognitive processes in a laboratory behavioral pharmacological context. Differential-reinforcement-of-low-rates (DRL) is an operant timing schedule that requires animals to produce inter-response-times (IRTs) greater than a criterion temporal interval to obtain a reward. Because animals must temporally regulate their responses and internally estimate the criterion duration, successful performance on the DRL task is dependent on both temporal processing and controlled timing behaviors. Since individuals with schizophrenia exhibit temporal processing deficits (Carroll et al, 2008; Elveag et al, 2008; Tysk et al, 1990), the DRL schedule can be utilized to evaluate the effects of ARZ to attenuate timing behaviors in a laboratory animal model of psychosis. In the studies presented here, water-deprived male Sprague-Dawley rats were trained to perform a DRL-72 second schedule that was either signaled (DRLS-72; n = 8) or unsignaled (DRLU-72; n = 8). Upon making a correct response (IRT ≥ 72s), rats were given a small amount (0.06mL) of distilled water as reinforcement. Subjects were trained ...