Role of the GABA a and GABA b receptors of the central nucleus of the amygdala in compulsive cocaine-seeking behavior in
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ORIGINAL INVESTIGATION
Role of the GABAa and GABAb receptors of the central nucleus of the amygdala in compulsive cocaine-seeking behavior in male rats WenLin Sun 1
&
Matt B. Yuill 1
Received: 27 December 2019 / Accepted: 24 August 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Rationale Compulsive cocaine use, defined as the continued use despite the dire consequences, is a hallmark of cocaine addiction. Thus, understanding the brain mechanism regulating the compulsive cocaine-seeking and cocaine-taking behaviors is essential to understand cocaine addiction and the key to identification of the molecular targets for the development of medications against this condition. Objective This study aimed to determine how the GABAa and GABAb receptors of the central nucleus of the amygdala (CeA) regulate the compulsive cocaine-seeking behavior. Methods Male Wistar outbred rats were trained to self-administer intravenous cocaine (0.4 mg/kg/infusion) under a chained schedule. The compulsive cocaine-seeking behavior was measured as the cocaine-seeking behavior in the face of footshock punishment. The role of the GABA receptors of CeA in the regulation of such behavior was determined by measuring the dosedependent effects of the GABAa agonist muscimol or the GABAb agonist baclofen bilaterally microinjected into the CeA on the punished cocaine-seeking behavior. Results The cocaine-seeking behavior was inhibited by footshock punishment in an intensity-dependent manner. Both muscimol and baclofen dose-dependently increased the punished cocaine-seeking behavior. However, the potency of muscimol but not baclofen was negatively correlated with the effects of punishment. Conclusion These data indicate that the CeA GABAa receptors play a key role in the regulation of the compulsive cocaineseeking behavior and suggest that an increase in the function of the GABAa receptors possibly induced by cocaine or genetic factors may be an important mechanism involved in the development of or vulnerability to the compulsive cocaine use and addiction. Keywords Punishment . Self-administration . Microinjection . Muscimol . Baclofen
Introduction Recreational cocaine use gradually becomes compulsive, indicated by the continued use despite the negative consequences. Such a transition suggests a breakdown of the brain mechanism involved in the regulation of cocaine use and is deemed as a key sign of cocaine addiction (American Psychiatric Association 2013). Thus, understanding the neural mechanism underlying the compulsive cocaine use will provide key insights into cocaine addiction and lead to the * WenLin Sun [email protected] 1
Department of Pharmacology, University of Tennessee Health Science Center, 71 S. Manassas, Memphis, TN 38103, USA
discovery of the druggable targets for the development of medications against this condition. The negative or aversive consequences associated with behavior typically decrease the probability of future occurrence of the behavior, a process referred to as punishment. The apparent la
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