Chronic cocaine self-administration attenuates the anxiogenic-like and stress potentiating effects of the benzodiazepine inverse agonist, FG 7142

Abstract

Stress is a well-known risk factor in relapse to drug abuse. Several forms of stress in animals have been used with varied degrees of success to elicit reinstatement of drug-seeking after chronic drug self-administration. Here, we tested the ability of the benzodiazepine (BZ) inverse agonist, FG 7142, to elicit anxiety-like behavior and potentiate stress responses in rats as measured by standard behavioral and hormonal indices and for its ability to affect reinstatement of cocaine-seeking in rats with a prior history of cocaine self-administration. FG 7142 elicited anxiety-like behavior on the elevated plus maze (EPM) in cocaine-naïve rats, and cocaine-naïve rats injected with FG 7142 exhibited increased plasma corticosterone levels following EPM exposure. However, in animals with a history of cocaine self-administration, FG 7142 failed to affect elevated plus maze performance and did not affect plasma corticosterone response to the EPM. Furthermore, FG 7142 failed to reinstate cocaine-seeking, nor did it alter conditioned cue-induced reinstatement. These data indicate that the anxiety-related and stress potentiating qualities of BZ inverse agonism are attenuated in cocaine-experienced animals and do not lead to reinstatement of cocaine-seeking.