Effects of haloperidol and clozapine on tongue dynamics during licking in CD-1, BALB/c and C57BL/6 mice

Rationale: In an initial effort to describe how genetic background influenc es the differential motor effects of haloperidol, a drug with high extrapyr amidal side effect (EPS) liability, and clozapine, an antipsychotic low in EPS, both drugs were studied in inbred strains of mice (BALB/c and C57BL/6) previously shown to have differential sensitivities to haloperidol. Object ives: Behavioral differences in lick dynamics for male BALB/c, C57BL/6 and CD-1 (an outbred strain) were characterized. Effects of dose ranges of halo peridol and clozapine were then evaluated in the three strains. Methods: Th e mice learned to lick milk from a force-sensing disk during daily 2-min se ssions, while a computer counted the number of licks and measured lick peak force and lick rhythm. After training, acute doses of haloperidol (0.08-2. 0 mg/kg) or clozapine (0.5-8.0 mg/kg) were administered i.p. 45 min before sessions. Results. Prior to drug treatment, substantial quantitative strain differences in licking behavior were observed: C57BL/6 mice made fewer lic ks, licked with lower peak force per lick, and had a slower lick rhythm tha n the BALB/c and CD-1 mice. As in rats, clozapine slowed the lick rhythm in all three mouse strains much more than haloperidol did. Haloperidol produc ed a 50% greater suppression of number of licks in BALB/c than in C57BL/6 m ice (ED50 values were 0.82 mg/kg and 1.22 mg/kg, respectively). For clozapi ne, lick suppression was greater in the C57BL/6 than in the BALB/c strain ( ED50 values were 1.88 mg/kg and 2.65 mg/kg, respectively). Among the three strains examined, CD-1 was the most sensitive to haloperidol's suppression of licking, while its sensitivity to clozapine's lick-suppressing effect wa s similar to C57BL/6 mice. Clozapine lowered the lick peak force in the CD- 1 and BALB/c strains more than in the C57BL/6 strain. Conclusions: Overall, the results suggest that genetic variables may influence both mice's tongu e dynamics and their alteration by both typical and atypical antipsychotic drugs. In addition, while the BALB/c strain was more sensitive to haloperid ol's lick-disruptive effects than the C57BL/6 strain, the size of the diffe rence between strains was much smaller than the reported difference between the strains in the catalepsy test.