Upregulation of postsynaptic dopamine receptors in the striatum does not influence haloperidol-induced catalepsy in mice.
The incidence of haloperidol-induced catalepsy was investigated in mice whose postsynaptic dopamine (DA) receptors in the striatum had been upregulated by denervation with 6-hydroxydopamine (6-OHDA). In nonupregulated mice, which were injected with 6-OHDA 4 days before, DA in the striatum fell to 21% of the level found in vehicle-injected mice but [3H]spiperone binding to the membrane of the striatum did not increase. In upregulated mice, which were injected with 6-OHDA 28 days before, DA was at 24% and [3H]spiperone binding increased by 15%. The ED50 values (with 95% confidence limits) for haloperidol-induced catalepsy in nonupregulated mice and that in upregulated mice was 0.40 mg/kg (0.25-0.65 mg/kg) and 0.29 mg/kg (0.16-0.51 mg/kg), respectively. There was no significant difference in the incidence of catalepsy between the two groups of mice. This suggests that the intensity of catalepsy produced by the DA receptor blockade may be unaltered even when the density of receptors increases.
Iwata
S
S
Department of Pharmacology, Faculty of Medicine, Kagoshima University, Japan.
Izumi
K
K
Nomoto
M
M
D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism; D002375:Catalepsy / Q000139:chemically induced / Q000503:physiopathology*; D003342:Corpus Striatum / Q000187:drug effects*; D006220:Haloperidol; D007700:Kinetics; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009419:Nerve Tissue Proteins / Q000378:metabolism; D016627:Oxidopamine / Q000494:pharmacology; D011954:Receptors, Dopamine / Q000187:drug effects*; D013134:Spiperone / Q000378:metabolism; D013569:Synapses / Q000187:drug effects / Q000502:physiology; D015854:Up-Regulation / Q000187:drug effects*
D015306:Biogenic Monoamines; D009419:Nerve Tissue Proteins; D011954:Receptors, Dopamine; D013134:Spiperone; D016627:Oxidopamine; D006220:Haloperidol