Differential roles of GABAB1 subunit isoforms on locomotor responses to acute and repeated administration of cocaine

Jacobson, Laura H. and Sweeney, Fabian F. and Kaupmann, Klemens and O'Leary, Olivia F. and Gassmann, Martin and Bettler, Bernhard and Cryan, John F.. (2016) Differential roles of GABAB1 subunit isoforms on locomotor responses to acute and repeated administration of cocaine. Behavioral Brain Research, 298 (Pt B). pp. 12-16.

Full text not available from this repository.

Official URL: https://edoc.unibas.ch/61399/

Downloads: Statistics Overview


GABAB receptors are crucial modulators of the behavioural effects of drug abuse, and agonists and positive allosteric modulators show promise as pharmacological strategies for anti-addiction therapeutics. GABAB receptors are functional heterodimers of GABAB1 and GABAB2 subunits. The predominant neuronal GABAB1 subunit isoforms are GABAB1a and GABAB1b. Selective ablation of these isoforms in mice revealed differential behavioural responses in fear, cognition and stress sensitivity. However, the influence of the two GABAB1 isoforms on responses to drugs of abuse is unclear. Therefore we examined the responses of GABAB1 subunit isoform null mice to cocaine in acute locomotor activity and conditioned place preference (CPP) paradigms. During habituation for the acute locomotor activity assay, GABAB1b(-/-) mice showed higher levels of locomotor activity relative to wild-type (WT) and GABAB1a(-/-) mice, in accordance with previous studies. Acute cocaine (10 mg/kg) increased locomotor activity in habituated mice of all three genotypes, with GABAB1a(-/-) mice showing sustained hyperlocomotor responses 30 min after cocaine relative to WT and GABAB1b(-/-) mice. No genotypes demonstrated a cocaine-induced place preference, however, GABAB1a(-/-) mice demonstrated enhanced locomotor sensitisation to chronic cocaine in the CPP paradigm in comparison to WT mice, whereas GABAB1b(-/-) mice failed to develop locomotor sensitisation, despite higher levels of basal locomotor activity. These findings indicate that GABAB1a and GABAB1b isoforms differentially regulate behavioural responses to cocaine, with deletion of GABAB1a enhancing cocaine-induced locomotor activity and deletion of GABAB1b protecting from cocaine-induced sensitisation.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Division of Physiology > Molecular Neurobiology Synaptic Plasticity (Bettler)
UniBasel Contributors:Bettler, Bernhard
Item Type:Article, refereed
Article Subtype:Research Article
ISSN:1872-7549 (Electronic) 0166-4328 (Linking)
Note:Publication type according to Uni Basel Research Database: Journal article
Related URLs:
Identification Number:
Last Modified:19 Jan 2019 18:27
Deposited On:19 Jan 2019 18:27

Repository Staff Only: item control page