The involvement of serotonergic neurons in the central nervous system as the possible mechanism for slow head-shaking behavior induced by methamphetamine in rats.

Following the IV administration of d-methamphetamine (MA), rats showed slow head shaking (SHS) and stereotyped gnawing (SG) behaviors in a dose-dependent manner. Methysergide, cyrpoheptadine, and p-chlorophenylalanine given intracerebroventricularly (ICV) or systemically significantly blocked SHS behavior induced by 10 mg/kg MA. Combined administration of L-5-hydroxytryptophan and peripheral decarboxylase inhibitor (Ro 4-4602) enhanced SHS behavior. Tyrosine hydroxylase inhibitor (H44/68) blocked SG behaviors, but dopamine-beta-hydroxylase inhibitors (FLA 63 and U-14, 624) and combined administration of L-3,4-dihydroxyphenylalanine and Ro-4-4602 enhanced it. These drugs did not affect SHS behavior. Phentolamine, phenoxybenzamine, clonidine, isoproterenol, and propranolol given ICV or systemically showed no effect on either SHS or SG behaviors. These results suggest that SHS behavior is produced by the activation of seronergic neurons in the central nervous system and are consistent with the view that SG behaviors are mediated through the release of dopamine. Some neuroleptics inhibited SHS as well as SG behaviors, but the older of inhibitory activity of neuroleptics onSHS behavior was quite different from their effects on SG behaviors induced by MA or apomorphine.