Peptide N- and P/Q-type Ca2+ blockers inhibit stimulant-induced hyperactivity in mice.
omega-Conotoxin GVIA and omega-agatoxin IVA are specific peptide blockers of N- and P/Q-type calcium channel, respectively. Effects of their intracerebroventricular injection (1-3 pmol/mouse) on psychostimulant-induced hyperactivity were investigated in mice. omega-Conotoxin GVIA antagonized methylphenidate-, methamphetamine- and phencyclidine-induced hyperactivity in a dose-dependent manner. omega-Agatoxin IVA blocked methylphenidate-induced but not methamphetamine- or phencyclidine-induced hyperactivity. Neither peptides showed any effect on apomorphine-induced hyperactivity or spontaneous activity, suggesting that the inhibitory effects on psychostimulant-induced hyperactivity are not due to dopamine receptor blockage or nonspecific behavioral depression. Antagonism of calcium channels, particularly N-type, may ameliorate activation of the dopaminergic system induced by increased dopamine release.
Tsukuba Research Laboratories, Eisai Co., Ltd., Ibaraki, Japan. h1-ogura@eisai.co.jp
H
H
Ogura
Y
Y
Furuya
T
T
Teramoto
T
T
Niidome
Y
Y
Nishizawa
Y
Y
Yamanishi
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D006948:Hyperkinesis / Q000139:chemically induced / Q000378:metabolism*; D007276:Injections, Intraventricular; D008694:Methamphetamine / Q000494:pharmacology; D008774:Methylphenidate / Q000494:pharmacology; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D010455:Peptides / Q000494:pharmacology*; D010622:Phencyclidine / Q000494:pharmacology; D013111:Spider Venoms / Q000494:pharmacology; D020867:omega-Agatoxin IVA; D020866:omega-Conotoxin GVIA
D002121:Calcium Channel Blockers; D000697:Central Nervous System Stimulants; D010455:Peptides; D013111:Spider Venoms; D020867:omega-Agatoxin IVA; D008774:Methylphenidate; D008694:Methamphetamine; D020866:omega-Conotoxin GVIA; D010622:Phencyclidine