The enhancement of the hypomotility induced by small doses of haloperidol in the phase of dopaminergic supersensitivity in mice.
Dopaminergic supersensitivity in mice was induced by pretreatment with a single injection of haloperidol (4.8 mg/kg). After the pretreatment, further treatment with haloperidol (0.6 or 0.01 mg/kg) was made at varying intervals, and catalepsy, locomotor activity and homovanillic acid (HVA) were measured. The intensity of the supersensitivity was evaluated by enhanced apomorphine (1 mg/kg)-induced climbing behavior. Supersensitivity was displayed on the 2nd and the 4th day. The cataleptogenic effect of haloperidol (0.6 mg/kg) was significantly weakened on the 1st, 2nd and 4th days. The motor inhibitory effect of haloperidol (0.01 mg/kg) increased on the 1st, 2nd and 4th days. Homovanillic acid was measured in the striatum and the prefrontal cortex on the 2nd day. Haloperidol (0.6 mg/kg) increased the concentrations of HVA in both regions of the brain. The increase in the concentrations of HVA in the striatum was blunted after the pretreatment, but such tolerance did not develop in the prefrontal cortex. Haloperidol (0.01 mg/kg) did not influence the concentration of HVA in both regions. These results suggest that the behavioral effect of a small dose of haloperidol may be enhanced, rather than reduced, in the phase of supersensitivity.
Masuda
Y
Y
Department of Pharmacology, School of Dentistry, Iwate Medical University, Morioka, Japan.
Murai
S
S
Saito
H
H
Abe
E
E
Fujiwara
H
H
Kohori
I
I
Itoh
T
T
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D002375:Catalepsy / Q000139:chemically induced / Q000503:physiopathology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000502:physiology*; D006220:Haloperidol / Q000494:pharmacology*; D006719:Homovanillic Acid / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000187:drug effects*; D012016:Reference Values
D006220:Haloperidol; D001058:Apomorphine; D004298:Dopamine; D006719:Homovanillic Acid