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

• Published in: Pharmacology, biochemistry and behavior biochemistry and behavior, 2011-09, Vol.99 (3), p.408-413
• Main Authors: Waters, R. Parrish, See, Ronald E.
• Format: Article
• Language: English
• Subjects: Animals; Anxiety - blood; Anxiety - chemically induced; Anxiety - prevention & control; Behavior, Addictive - blood; Behavior, Addictive - drug therapy; Benzodiazepine; Benzodiazepines - agonists; Biological and medical sciences; Carbolines - toxicity; Cocaine; Cocaine - administration & dosage; Corticosterone - blood; Dose-Response Relationship, Drug; FG 7142; Male; Medical sciences; Neuropharmacology; Pharmacology. Drug treatments; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Rats; Rats, Sprague-Dawley; Receptors, GABA-A - physiology; Reinstatement; Relapse; Self Administration; Stress, Psychological - blood; Stress, Psychological - chemically induced; Stress, Psychological - prevention & control
• ISSN: 0091-3057; 1873-5177
• DOI: 10.1016/j.pbb.2011.05.021

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. ► Relapse to cocaine abuse can be elicited by stress. ► Pharmacological stressors can serve as probes in understanding this phenomenon. ► FG 7142 potentiates the stress response of rats to the EPM. ► These effects are absent in cocaine trained rats. ► FG 7142 does not influence extinguished cocaine seeking behavior.