Pharmacokinetics and effects of haloperidol in the isolated mouse

The pharmacokinetic behaviour of haloperidol (0.6 mg/kg s.c.) was studied in grouped and 4-week isolated male mice of the CF-1 strain (24 h observation; gas chromatography, NPFID). Maximal drug levels occurred in serum within 2 min and in whole brain after 15 min. The elimination from serum and brain was biphasic with larger t1/2 values for brain. There was an accumulation of haloperidol in brain up to 40 times of the serum level. Isolation resulted in a more rapid first phase of elimination from serum, provided the animals were tested for aggressivity immediately before the administration of the drug. The minimal effective (i.e. cataleptogenic) brain level of haloperidol was approximately 0.1 microgram/g wet weight. Haloperidol-induced catalepsy was (after 1 h) in isolated mice weaker than in grouped mice; this applied to animals of both the CF-1 and the NMRI strain. The catalepsy disappeared after 6 h. The antagonism by haloperidol of the stereotyped gnawing (induced by methylphenidate, 30 and 50 mg/kg, i.p., NMRI mice) likewise lasted for 6 h. Therefore, the cataleptic effects, but not the brain levels of haloperidol, are influenced by isolation and aggression in mice.