The impact of GABAB receptors and their pharmacological stimulation on cocaine reinforcement and drug-seeking behaviors in a rat model of depression

Depression and cocaine use disorder represent frequent co-current diagnoses and the GABAB receptors are involved in both conditions. This research involved the application of the animal model of depression (bulbectomy, OBX) and cocaine use disorder (self-administration) to assess the efficiency of G...

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Bibliographic Details
Published in:European journal of pharmacology 2020-09, Vol.883, p.173324-173324, Article 173324
Main Authors: Gawlińska, Kinga, Jastrzębska, Joanna, Gamberini, Sara, Gawliński, Dawid, Pieniążek, Renata, Suder, Agata, Wydra, Karolina, Frankowska, Małgorzata
Format: Article
Language:English
Subjects:
Bulbectomy
Cocaine self-administration
GABAB receptor Agonists
GABAB1 subunit
GABAB2 subunit
Reinstatement
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Summary:Depression and cocaine use disorder represent frequent co-current diagnoses and the GABAB receptors are involved in both conditions. This research involved the application of the animal model of depression (bulbectomy, OBX) and cocaine use disorder (self-administration) to assess the efficiency of GABAB receptor agonists, baclofen and SKF-97541, on cocaine rewarding property and reinforcement of seeking-behaviors in rats with depressive phenotype. Additionally, we applied immunoreactive techniques to determine changes in the expression of GABAB receptor subunit 1 and 2 in rats with depression and cocaine addiction. The results obtained the study illustrate that the GABAB receptor agonists reduced the rewarding property of cocaine in both OBX and control (SHAM) rats. Both agonists significantly reduced cue- and cocaine-induced reinstatement in both groups. This is the first report demonstrating a different impact of cocaine abuse on GABAB receptor levels in depressed animals. It was documented that the expression of GABAB1 subunit in the infralimbic cortex increased during self-administration and extinction training in OBX animals. The lower level of expression for this subunit in addictive SHAM rats during self-administration, and increased in extinguished addictive OBX rats was found in the ventrolateral striatum. The expression of GABAB2 subunit changed only in the case of cocaine self-administration paradigm, as a decline of the subunit level in the nucleus accumbens and ventral hippocampus was observed only in OBX rats. The relevance of GABAB receptors in depression and addiction comorbidity is clearly implicated and can open a new era of drug discovery for individuals with dual diagnosis. [Display omitted] •GABAB receptor agonists reduce cocaine addiction in rats with depressive phenotype.•GABAB2 receptor subunit is related with depressive-like phenotype.•GABAB1 receptor subunit is related to addictive behavior in depressive rats.
ISSN:0014-2999
1879-0712
DOI:10.1016/j.ejphar.2020.173324