Ontogeny of cocaine hyperactivity and conditioned place preference in mice

Abstract

Conditioned place preference (CPP) procedures using jointly visual and tactile cues (white compartment with a wide-mesh metal floor versus black compartment with a narrow-mesh floor) were employed to assess the ontogenetic pattern of cocaine reinforcing properties in outbred CD1 mice. A classical 11-day-long schedule, in which the drug experience occurred in the initially less-preferred compartment (“biased” procedure, Spyraki 1988), served to study cocaine (0, 1, 5, or 25 mg/kg IP repeated four times at 48 h intervals) during the early postweaning stage (21–32 days). The result was a fully-fledged CPP at all cocaine doses. A subsequent experiment used a shortened (4-day) “unbiased” CPP schedule (animals assigned at random to drug experience in one or the other compartment); this enabled an assessment of the ontogenetic pattern of the drug action (single treatment, same dose range) in pups of both sexes at three different developmental ages (14–17, 21–24, or 28–31 days). At the 25 mg/kg dose, CPP developed in animals of all ages, while the 5 mg/kg dose was effective only in 21–24 day pups and the 1 mg/kg dose was ineffective. No significant sex differences were found, but the use of the unbiased procedure enabled a demonstration of an interaction between treatment, age, and type of CS. At the preweaning stage, CPP was due mainly to an increased preference for the black/narrowmesh compartment, while at the early postweaning stage it consisted mainly of an increased preference for the white/wide-mesh compartment; at the late postweaning stage the cue and the treatment factor did not interact. At all ages tested cocaine induced a dose-dependent increase in locomotor activity which was much more marked at both post-weaning stages than before weaning.