Periadolescent nicotine exposure produces sensitization to reinforcement by diazepam in the rat

Epidemiologic studies establish a relationship between nicotine use by adolescents and a subsequent involvement with drugs of abuse in adulthood. Recent research implicates the periadolescent period as a crucial time in development, during which nicotine use produces persistent adaptations that serve to predispose an individual to substance use. The present investigation evaluated the effects of periadolescent nicotine priming on young adult sensitization to reinforcement by a drug of abuse. Nicotine (0.4 mg/kg, intraperitoneal), mecamylamine (2 mg/kg, subcutaneous), mecamylamine and nicotine, or saline was administered as a once-daily injection to periadolescent (postnatal days 35-44) Sprague-Dawley male rats. The effects of periadolescent nicotine priming on reinforcement parameters in the young adult animal (postnatal day 80) were measured by conditioning a place preference with diazepam (1 mg/kg, subcutaneous). Rats were tested for place conditioning in a drug-free state. In contrast to other periadolescent treatment groups, rats treated with only nicotine during periadolescence showed a heterologous sensitization to the subthreshold dose of diazepam utilized during conditioning. Pretreatment with mecamylamine before periadolescent nicotine priming prevented the enhanced response to diazepam observed in the young adult animal. Priming with nicotine during late adolescence (postnatal days 60-69) failed to sensitize the adult rats to diazepam. This study supports a relationship between periadolescent nicotine priming and the production of persistent, behavioral adaptations in the young adult animal.