EFFECTS OF REPEATED TREATMENT WITH METHAMPHETAMINE PLUS SCOPOLAMINE AND METHAMPHETAMINE ON BEHAVIORAL SENSITIZATION AND CONDITIONING

This study compared repeated treatment with methamphetamine (4.0 mg/kg , i.p.) plus scopolamine (0.5 mg/kg, i.p.) and methamphetamine alone i n behavioral sensitization and drug conditioning with respect to a rec iprocal balance between the dopaminergic and cholinergic systems. Repe ated methamphetamine plus scopolamine treatment induced a more progres sive and enduring enhancement of stereotyped behavior than repeated me thamphetamine treatment. Methamphetamine plus scopolamine-induced ster eotyped behavior was reproduced by challenge injections of not only me thamphetamine plus scopolamine and methamphetamine, but also, to a les ser extent, by scopolamine challenges. The methamphetamine plus scopol amine-sensitized rats were conditioned to a low-frequency tone (300 Hz , 100 dB) as conditioned stimulus associated with the drug state. They responded to pairings of the tone and placebo injections, but not to the tone alone or the placebo alone. The methamphetamine-sensitized ra ts failed to exhibit conditioning. These results suggest that methamph etamine plus scopolamine-induced pronounced behavioral sensitization m ay produce an enhanced conditioning. Exteroceptive conditioned stimulu s-interoceptive unconditioned stimulus associations may provide an imp ortant source for drug conditioning. We concluded that behavioral sens itization may be mediated via a reciprocal balance between the dopamin ergic and cholinergic systems, in favor of a dopaminergic dominance. C onditioning to the drug-associated tone may operate via a reciprocal b alance between the dopaminergic and cholinergic systems.