[Cholinergic modulation on stereotyped behavior and behavioral hypersensitivity (reverse tolerance) in rats].

The failure in the mutual balance between striatal/mesolimbic dopaminergic neurons and the inhibitory system, and a decreased activity of mesocortical dopaminergic neurons may account for biological base of paranoid schizophrenia. We tested this hypothesis by investigating stereotyped behavior and "reverse tolerance" in dopaminergic supersensitivity co-existing with a low-level activity of the inhibitory cholinergic system induced by the chronic administration of methamphetamine (MAP) 4 mg/kg in combination with scopolamine (SCOP) 0.5 mg/kg, in male Wistar rats. For investigating the influence of mesocortical dopaminergic neurons, experiments were designed to compare these behavioral responses in isolated rats, in which the activity of mesocortical dopaminergic neurons seemed to be reduced, to those in group-housed rats. The treatment with MAP plus SCOP produced significantly more potent effect in enhancing stereotyped behavior and "reverse tolerance" than the treatment with MAP only. Stereotyped behavior and "reverse tolerance" induced by the MAP plus SCOP treatment were more intense in isolated rats than in grouped rats. Effects of haloperidol (1 mg/kg) and pimozide (2 mg/kg or 5 mg/kg) on stereotyped behavior were less in MAP plus SCOP treated rats and isolated rats. The data may support a working hypothesis.