Abstract

The two most concurrently used recreational drugs are EtOH and tobacco. Adolescence is the age of onset for use of both these drugs. We have previously found concurrent self‐administration of EtOH and nicotine (EtOH+Nic) is reinforcing in adolescent, but induces kappa‐opioid receptor (KOR)‐mediated aversion in adult rats. We also found acute administration of EtOH+Nic is anxiolytic in adolescents, but not adults. This study focused on the mechanism of action of EtOH+Nic anxiolysis in adolescents, and tested if the KOR has a role in the lack of effect in adults. We hypothesize that KOR activation prevents EtOH+Nic‐induced anxiolysis in adults. To test this, we pretreated male adolescent, aged postnatal day (P)29, and adult (P87) Sprague Dawley rats with the irreversible KOR antagonist, nor‐BNI (10 mg/kg, i.p.). Three days later, we acutely administered saline, or Nic (30 μg/kg) and EtOH (4 mg/kg), then monitored behavior in a novel open field for 30 minutes. Brains were immediately collected after the open field behavior experiment and processed for in situ hybridization for c‐fos mRNA. C‐fos is an immediate early gene commonly used as a neuronal activity marker. Anatomical analysis comparing c‐fos activation induced by acute EtOH+Nic will help understand the mechanism of action by which EtOH+Nic causes unique behaviors in adolescent rats, and how KOR is involved in EtOH+Nic aversion in adult rats.

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