title: 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.
authors.affiliation: Department of Neurosciences, Medical University of South Carolina, Charleston, SC 29425, USA.
authors.forename: R Parrish
authors.initials: RP
authors.lastname: Waters
authors.forename: Ronald E
authors.initials: RE
authors.lastname: See
mesh_terms: D000818:Animals; D001007:Anxiety / Q000097:blood / Q000139:chemically induced / Q000517:prevention & control*; D016739:Behavior, Addictive / Q000097:blood / Q000188:drug therapy; D001569:Benzodiazepines / Q000819:agonists*; D002243:Carbolines / Q000633:toxicity*; D003042:Cocaine / Q000008:administration & dosage*; D003345:Corticosterone / Q000097:blood; D004305:Dose-Response Relationship, Drug; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000502:physiology; D012646:Self Administration; D013315:Stress, Psychological / Q000097:blood / Q000139:chemically induced / Q000517:prevention & control*
chemical_list: D002243:Carbolines; D011963:Receptors, GABA-A; D001569:Benzodiazepines; C035874:FG 7142; D003042:Cocaine; D003345:Corticosterone