Behavioral responses induced by repeated treatment with methamphetamine alone and in combination with scopolamine in rats.

Repeated amphetamine (A) or methamphetamine (M) treatment induces behavioral sensitization and drug conditioning. The present study compared behavioral sensitization and drug conditioning between treatments with M combined with scopolamine (S) and M alone with respect to a reciprocal balance between the dopaminergic and inhibitory cholinergic systems in rats. Repeated treatment with M (4.0 mg/kg i.p.) combined with S (0.5 mg/kg i.p.) (MS) produced progressive enhancement of stereotyped behavior, compared with repeated M treatment alone. Repeated MS treatment induced focussed stereotyped behavior that was elicited by every challenge injection of not only MS and M, but also partially by S. MS- but not M-sensitized rats exhibited conditioned responses to a tone (300 Hz, 100 dB) associated with drug state, suggesting that MS-induced pronounced behavioral sensitization may lead to an enhanced conditioned response to the conditioned stimulus (CS) of a tone. It is suggested that MS-induced behavioral sensitization may be mediated via a reciprocal balance between the dopaminergic and cholinergic systems in favor of a dopaminergic dominance, and that such a balance may be involved in the conditioning to the drug-associated tone CS.