Potentiation of para-hydroxyamphetamine-induced head-twitch response by inhibition of monoamine oxidase type A in the brain.
After pretreatment with either clorgyline, a monoamine oxidase (MAO)-A-selective inhibitor, or pargyline, an MAO-B-selective inhibitor with less selectivity than l-deprenyl, i.c.v. administration of para-hydroxyamphetamine (p-OHA) significantly increased both the frequency and total number of head-twitches in mice. A typical MAO-B-selective inhibitor, l-deprenyl, however, did not change the total count of the p-OHA-induced head-twitch response (HTR). These effects were also found with fixed doses of the selective MAO inhibitors when p-OHA was varied. Administration of clorgyline (1 mg/kg) or pargyline (5 mg/kg) almost inhibited completely MAO-A in the mouse forebrain, and pargyline also almost inhibited completely MAO-B. l-Deprenyl, in contrast, almost inhibited completely MAO-B without affecting MAO-A activity. Systemic administration of l-5-hydroxytryptophan also induced HTR and the total number of twitches was enhanced by clorgyline, but not by pargyline or l-deprenyl. Chlorimipramine or cocaine significantly reduced p-OHA-induced HTR, suggesting an intraneuronal site of action. Together with the presence of considerable MAO-A in 5-hydroxytryptamine (5-HT) neurons of various animal species, and possible accumulation and subsequent monoamine-releasing properties of p-OHA, the present results indicate that p-OHA might induce the HTR by interaction with intraneuronally increased 5-HT. This mechanism probably results in 5-HT release onto the postsynaptic 5-HT2 receptors. Taken together, different roles of MAO-B in "the hyperactivity syndrome" and the HTR are discussed.
Tadano
T
T
Department of Pharmacology, Tohoku College of Pharmacy, Sendai, Japan.
Satoh
S
S
Satoh
N
N
Kisara
K
K
Arai
Y
Y
Kim
S K
SK
Kinemuchi
H
H
D000662:Amphetamines / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology*; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology*; D003010:Clorgyline / Q000494:pharmacology; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D010293:Pargyline / Q000494:pharmacology; D012642:Selegiline / Q000494:pharmacology; D013239:Stereotyped Behavior / Q000187:drug effects*; D010136:p-Hydroxyamphetamine / Q000008:administration & dosage / Q000494:pharmacology*
D000662:Amphetamines; D008996:Monoamine Oxidase Inhibitors; D012642:Selegiline; D010293:Pargyline; D008995:Monoamine Oxidase; D010136:p-Hydroxyamphetamine; D003010:Clorgyline