MORPHINE-INDUCED LONG-TERM SENSITIZATION TO THE LOCOMOTOR EFFECTS OF MORPHINE AND AMPHETAMINE DEPENDS ON THE TEMPORAL PATTERN OF THE PRETREATMENT REGIMEN

The development of behavioural sensitization is thought to depend on t he dose and temporal pattern of drug treatment. Previous studies have shown that two distinct morphine pretreatment regimens cause different long-term neuroadaptations in rat striatum. Therefore, in the present study the ability of these pretreatment regimens to induce long-term behavioural sensitization was investigated. One pretreatment regimen, termed ''chronic'', consisted of three daily injections, for 5 days, w ith escalating doses (10-50 mg/kg) of morphine, and the other, termed ''intermittent'', of 14 daily injections with morphine (10 mg/kg). Bot h intermittent and chronic morphine pretreatment caused sensitization to the locomotor effects of morphine, 3 weeks post-treatment, although the former induced a far greater level of sensitization. Moreover, 3 weeks post-treatment, intermittent, but not chronic, morphine pretreat ment induced cross-sensitization to the locomotor stimulant effects of amphetamine. Behavioural sensitization following intermittent morphin e pretreatment was clear-cut both 1 day and 3 weeks post-treatment, wh ile after 9 weeks, the locomotor effects of morphine were still slight ly augmented. It is concluded that intermittent morphine pretreatment is far more effective in inducing long-term behavioural sensitization than chronic morphine pretreatment.