Adolescent nicotine exposure enhances alcohol self‐administration, and subsequently affects extinction of conditioned fear response

Abstract

We have shown that nicotine (Nic) is a ‘gateway’ drug that sensitizes the adolescent brain to other abused drugs. Furthermore, alcohol exposure during development leads to neuroanatomical abnormalities and adverse behavior.We hypothesize that Nic acts as a ‘gateway’ for ethanol (EtOH) self‐administration (SA), and that development of the limbic circuitry can be altered by adolescent Nic and EtOH exposure. We thus tested the effect of brief, low‐dose Nic pretreatment on the acquisition of EtOH SA in adolescent and adult male rats, and then tested for extinction of conditioned fear response (CFR). Adolescent rats, aged postnatal day (P) 28, or adult P86 rats, were given 2 daily intravenous (IV) injections of Nic (0.03 mg/kg/0.1 ml) or saline for 4 consecutive days. At P32 and P90 animals were allowed to IVSA EtOH daily with escalating doses over 10 consecutive days. CFR testing occurred 1 week later.Nic pretreatment enhanced early acquisition of EtOH IVSA in adolescent rats, but not total intake in either age group. Wheareas there was no significant relationship between Nic or EtOH intake and CFR extinction in adult rats, there was an interaction between Nic and EtOH exposure in adolescents, with a significant decrease in CFR with increased EtOH intake. These data suggest that adolescent Nic exposure enhances initial acquisition of EtOH IVSA and that Nic and EtOH have lasting effects on limbic forebrain development.