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.