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/narrow-mesh 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.(ABSTRACT TRUNCATED AT 250 WORDS)