کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6256324 | 1289914 | 2016 | 5 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Short communicationDifferential roles of GABAB1 subunit isoforms on locomotor responses to acute and repeated administration of cocaine Short communicationDifferential roles of GABAB1 subunit isoforms on locomotor responses to acute and repeated administration of cocaine](/preview/png/6256324.png)
- We explored the role of GABAB1 subunit isoforms in responses to cocaine.
- GABAB1aâ/â mice showed elevated hyperlocomotion and sensitisation to cocaine.
- GABAB1bâ/â mice failed to develop locomotor sensitisation to repeated cocaine.
- GABAB1 isoforms differentially regulate behavioural responses to cocaine.
- The GABAB1b subunit isoform may be a target for treating drug addiction.
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, GABAB1bâ/â mice showed higher levels of locomotor activity relative to wild-type (WT) and GABAB1aâ/â mice, in accordance with previous studies. Acute cocaine (10Â mg/kg) increased locomotor activity in habituated mice of all three genotypes, with GABAB1aâ/â mice showing sustained hyperlocomotor responses 30Â min after cocaine relative to WT and GABAB1bâ/â mice. No genotypes demonstrated a cocaine-induced place preference, however, GABAB1aâ/â mice demonstrated enhanced locomotor sensitisation to chronic cocaine in the CPP paradigm in comparison to WT mice, whereas GABAB1bâ/â 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.
Journal: Behavioural Brain Research - Volume 298, Part B, 1 February 2016, Pages 12-16