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.