G Wang1, S C Fowler. 1. Department of Pharmacology and Toxicology, University of Kansas, Lawrence 66045, USA.
Abstract
RATIONALE: In an initial effort to describe how genetic background influences the differential motor effects of haloperidol, a drug with high extrapyramidal 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. OBJECTIVES: Behavioral differences in lick dynamics for male BALB/c, C57BL/6 and CD-1 (an outbred strain) were characterized. Effects of dose ranges of haloperidol and clozapine were then evaluated in the three strains. METHODS: The mice learned to lick milk from a force-sensing disk during daily 2-min sessions, 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 licks, licked with lower peak force per lick, and had a slower lick rhythm than 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 produced a 50% greater suppression of number of licks in BALB/c than in C57BL/6 mice (ED50 values were 0.82 mg/kg and 1.22 mg/kg, respectively). For clozapine, 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 was 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 tongue dynamics and their alteration by both typical and atypical antipsychotic drugs. In addition, while the BALB/c strain was more sensitive to haloperidol's lick-disruptive effects than the C57BL/6 strain, the size of the difference between strains was much smaller than the reported difference between the strains in the catalepsy test.
RATIONALE: In an initial effort to describe how genetic background influences the differential motor effects of haloperidol, a drug with high extrapyramidal 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. OBJECTIVES: Behavioral differences in lick dynamics for male BALB/c, C57BL/6 and CD-1 (an outbred strain) were characterized. Effects of dose ranges of haloperidol and clozapine were then evaluated in the three strains. METHODS: The mice learned to lick milk from a force-sensing disk during daily 2-min sessions, 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 licks, licked with lower peak force per lick, and had a slower lick rhythm than the BALB/c and CD-1mice. As in rats, clozapine slowed the lick rhythm in all three mouse strains much more than haloperidol did. Haloperidol produced a 50% greater suppression of number of licks in BALB/c than in C57BL/6 mice (ED50 values were 0.82 mg/kg and 1.22 mg/kg, respectively). For clozapine, 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 was 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 tongue dynamics and their alteration by both typical and atypical antipsychotic drugs. In addition, while the BALB/c strain was more sensitive to haloperidol's lick-disruptive effects than the C57BL/6 strain, the size of the difference between strains was much smaller than the reported difference between the strains in the catalepsy test.
Authors: Susan E Smittkamp; Heather N Spalding; Jordan W Brown; Anisha A Gupte; Jie Chen; Hiroshi Nishimune; Paige C Geiger; John A Stanford Journal: Behav Brain Res Date: 2010-03-06 Impact factor: 3.332
Authors: John D Boughter; Megan K Mulligan; Steven J St John; Kenichi Tokita; Lu Lu; Detlef H Heck; Robert W Williams Journal: PLoS One Date: 2012-05-31 Impact factor: 3.240