Effect of β3 adrenoceptor activation in the basolateral amygdala on ethanol seeking behaviors

Rationale The interaction between ethanol (EtOH) and anxiety plays an integral role in the development and maintenance of alcoholism. Many medications in pre-clinical or clinical trials for the treatment of alcoholism share anxiolytic properties. However, these drugs typically have untoward side eff...

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Bibliographic Details
Published in:Psychopharmacology 2014, Vol.231 (1), p.293-303
Main Authors: Butler, T. R., Chappell, A. M., Weiner, J. L.
Format: Article
Language:English
Subjects:
Adrenergic beta-3 Receptor Agonists - administration & dosage
Adrenergic beta-3 Receptor Agonists - pharmacology
Alcohol Drinking - psychology
Alcoholism
Amygdala (Brain)
Amygdala - drug effects
Animals
Anxiety
Biomedical and Life Sciences
Biomedicine
Choice Behavior
Complications and side effects
Conditioning, Operant - drug effects
Development and progression
Drug-Seeking Behavior - drug effects
Ethanolamines - administration & dosage
Ethanolamines - pharmacology
Extinction, Psychological - drug effects
Genetic aspects
Male
Microinjections
Motivation - drug effects
Neurosciences
Original Investigation
Pharmacology/Toxicology
Physiological aspects
Psychiatry
Rats
Rats, Long-Evans
Risk factors
Sucrose - pharmacology
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Summary:Rationale The interaction between ethanol (EtOH) and anxiety plays an integral role in the development and maintenance of alcoholism. Many medications in pre-clinical or clinical trials for the treatment of alcoholism share anxiolytic properties. However, these drugs typically have untoward side effects, such as sedation or impairment of motor function that may limit their clinical use. We have recently demonstrated that BRL 37344 (BRL), a selective β3-adrenoceptor (AR) agonist, enhances a discrete population of GABAergic synapses in the basolateral amygdala (BLA) that mediates feed-forward inhibition from lateral paracapsular (LPC) GABAergic interneurons onto BLA pyramidal cells. Behavioral studies revealed that intra-BLA infusion of BRL significantly reduced measures of unconditioned anxiety-like behavior without locomotor depressant effects. Objectives The present studies tested the effect of BRL (0.1, 0.5, or 1.0 μg/side) on EtOH self-administration using an intermittent access home cage two-bottle choice procedure and limited access operant responding for EtOH or sucrose. Results Intra-BLA infusion of BRL did not reduce home cage, intermittent EtOH self-administration. However, using an operant procedure that permits the discrete assessment of appetitive (seeking) and consummatory measures of EtOH self-administration, BRL reduced measures of EtOH and sucrose seeking, but selectively reduced operant responding for EtOH during extinction probe trials. BRL had no effect on consummatory behaviors for EtOH or sucrose. Conclusions Together, these data suggest that intra-BLA infusion of BRL significantly reduces motivation to seek EtOH and provide initial evidence that β3-ARs and LPC GABAergic synapses may represent promising targets for the development of novel pharmacotherapies for the treatment of alcoholism.
ISSN:0033-3158
1432-2072
DOI:10.1007/s00213-013-3238-y