Differential behavioral and neurochemical effects of nicotine treatment in adolescent and adult rats

Abstract

Epidemiological studies have established that drug use in adolescence is initiated with tobacco and alcohol and progresses to illicit drugs. These findings have led to the hypothesis that alcohol and tobacco are ‘gateway’ drugs that sensitize reward pathways to the effects of illicit drugs like cocaine. We have previously shown that subchronic nicotine pretreatment enhances acquisition of cocaine self‐administration in adolescent, but not adult, rats (McQuown et al., 2007). The present study was designed to determine whether sensitization to cocaine's reinforcing effects was accompanied by an increase in locomotor response. In addition, we probed for underlying neurochemical changes in the dopamine system caused by this nicotine pretreatment. Male Sprague‐Dawley rats at P28 or P86 were given daily i.v. injections of nicotine or saline spaced 1 min apart for four days. At P32 and P90, one group of rats was sacrificed for radioligand binding. The second group received i.v. cocaine (2 × 0.2‐ or 0.5 mg/kg/0.1 ml) or saline infusions and were placed in a novel locomotor chamber. A third group was treated 3 days with i.v. cocaine or saline after a 30 min habituation in the locomotor box. At P36 or P95, all animals in this group were given a challenge of low dose cocaine and locomotor activity was observed. Nicotine pretreatment had no effect on locomotor response to acute cocaine‐induced locomotor activity at either age. Repeated cocaine exposure produced locomotor sensitization to both doses of cocaine in nicotine‐pretreated animals (p < 0.05). However, only nicotine‐pretreated adolescents expressed a sensitized response on challenge day. Neurochemical analyses revealed age‐specific changes in dopamine D3 receptors. Overall, these findings provide evidence of a differential effect of nicotine on adolescent and adult brain.