(534.3) Does clozapine affect the discriminative stimulus effects of food deprivation in rats trained to discriminate between 2 and 22 hours food deprivation?

Poster Board Number: B34

Erika Cedarbloom (University of Wisconsin-Eau Claire), Sam Petit (University of Wisconsin-Eau Claire), Regina Grosland (University of Wisconsin-Eau Claire), Keelin Norman-Klatt (University of Wisconsin-Eau Claire), Abigail Vigil (University of Wisconsin-Eau Claire), Dane Detert (University of Wisconsin-Eau Claire), Courtney Passint (University of Wisconsin-Eau Claire), Tatum Sweeney (University of Wisconsin-Eau Claire), Haley Quandt (University of Wisconsin-Eau Claire), David Jewett (University of Wisconsin-Eau Claire)

In humans, weight gain is a side effect of several atypical antipsychotics. Previous research with rodents indicates clozapine may increase food consumption for the first 2-4 hours after injection (Antelman et al. 1977; Benvenga amp; Leander 1997; Lee amp; Clifton 2002) as well as increase motivation to acquire food under a progressive ratio schedule (Abela et al. 2020; Loh et al. 1992; Mobini et al. 2000). In other studies, however, clozapine has been shown to reduce response rates in lever pressing operant procedures (Ford et al., 1997; Kaempf amp; Porter, 1997; Varvel et al., 2002; Wiley et al., 1994; Abela 2020) and decrease food intake in rodents (Baptista et al., 1993). The current study investigated if clozapine would affect the discriminative stimulus effects of food deprivation. Male, Sprague-Dawley rats (n = 11) were trained to discriminate 22 hrs of food deprivation from 2 hrs of food deprivation in a two-lever, operant choice task. Rats were trained to respond on the right lever after 2 hrs of food deprivation to earn a 45 mg food pellet under an FR 15 schedule. Left lever presses were punished with 8 seconds of darkness. Under 22 hr deprivation conditions, the contingencies were reversed (left lever presses were reinforced with food delivery and right lever presses resulted in 8 seconds of darkness). Training sessions lasted until subjects earned 10 reinforcers or 15 minutes elapsed. Acquisition of discrimination was defined as 80% or greater condition appropriate responding both before the first reinforcer was earned and for the entire session for 8 out of 10 consecutive days. After acquiring the discrimination, subjects were food deprived for 2 or 22 hrs and administered clozapine (1.0 - 5.6 mg/kg, s.c.). or vehicle (30% DMSO; 1.0 ml/kg, s.c.). During test sessions, responses toward either lever were reinforced under the FR 15. The session lasted until subjects earned 5 reinforcers or 5 minutes elapsed, whichever occurred first. The discriminative stimulus effects of food deprivation and response rates were assessed every 15 min for the succeeding 2 hrs. After test sessions, each subjects’ food intake was recorded for 1 hour.  Clozapine had no effect on the discriminative stimulus effects of 2 hr deprivation, however, clozapine (1.0 - 5.6 mg/kg) significantly decreased response rates. After 22 hrs food deprivation, clozapine (1.0 - 5.6 mg/kg) significantly decreased % 22 hr deprivation-appropriate responding. Response rates were significantly increased by 1.0 mg/kg clozapine, whereas response rates were decreased by 5.6 mg/kg clozapine compared to rates of responding following 30% DMSO. Clozapine (3.2 - 5.6 mg/kg) decreased food intake in rats under both food deprivation conditions. These data provide further support for the notion that clozapine decreases feeding-related behaviors in rats.

The University of Wisconsin-Eau Claire Center of Excellence for Faculty and Student Undergraduate Research Collaboration
The University of Wisconsin-Eau Claire Summer Research Experiences for Undergraduates Grant