ONTOGENY OF BEHAVIORAL SENSITIZATION TO COCAINE

The ontogeny of the behavioral effects of acute cocaine administration and behavioral sensitization to cocaine in rat pups was investigated. Acute behavior stimulating effects of cocaine were observed in pups a s young as 7 postnatal days (PND) old, although they needed a higher d ose of cocaine than adult rats to evoke the same motor effects. An adu lt dose-response curve pattern of stereotypy and locomotion to acute c ocaine treatment was observed at PND 21, and of rearing at PND 28. Rat s aged PND 7, 14, 21, 28, and 56 received repeated injections of salin e or cocaine (15 mg/kg) twice a day for 5 consecutive days. After a 3- week period of abstinence, sensitization to a challenge dose of cocain e was assessed. Cocaine-induced stereotyped behavior was enhanced sign ificantly only in rats in which cocaine pretreatment was initiated on PND 21, 28, and 56, but not earlier on PND 7 and 14. Adult female rats given repeated cocaine injections on PND 56-60 showed significantly g reater sensitization than males, but no such sex difference was observ ed in pups given cocaine repeatedly on PND 21-25 or 28-32. These resul ts show clearly that cocaine-induced behavioral sensitization in rats occurred only when subchronic cocaine administration was commenced on PND 21 or later.