| First Author | Sah A | Year | 2021 |
| Journal | Neuropharmacology | Volume | 198 |
| Pages | 108752 | PubMed ID | 34390690 |
| Mgi Jnum | J:317306 | Mgi Id | MGI:6789765 |
| Doi | 10.1016/j.neuropharm.2021.108752 | Citation | Sah A, et al. (2021) Neuronal correlates underlying the role of the zinc sensing receptor (GPR39) in passive-coping behaviour. Neuropharmacology 198:108752 |
| abstractText | The Zn(2+) receptor GPR39 is proposed to be involved in the pathophysiology of depression. GPR39 knockout (KO) animals show depressive- and anxiety-like behaviour, and resistance to conventional monoamine-based antidepressants. However, it is unclear as to which brain regions are involved in the pro-depressive phenotype of GPR39KO mice and the resistance to monoamine-targeting antidepressant treatment. Our current study confirmed previous results, showing that mice lacking GPR39 display enhanced passive coping-like behaviour compared with their wild-type controls. Furthermore, this study shows for the first time that GPR39KO displayed aberrant challenge-induced neuronal activity in key brain regions associated with passive coping behaviour. Imipramine induced only a marginal reduction in the enhanced passive coping behaviour in GPR39KO mice, which was associated with attenuation of the hyperactive prefrontal cortex. Similarly, the aberrant activity within the amygdalar subregions was normalized following imipramine treatment in the GPR39KO mice, indicating that imipramine mediates these effects independently of GPR39 in the prefrontal cortex and amygdala. However, imipramine failed to modulate the aberrant brain activity in other brain regions, such as the anterior CA3 and the dentate gyrus, in GPR39KO mice. Normalization of aberrant activity in these areas has been shown previously to accompany successful behavioural effects of antidepressants. Taken together, our data suggest that monoamine-based antidepressants such as imipramine exert their action via GPR39-dependent and -independent pathways. Failure to modulate passive-coping related aberrant activity in important brain areas of the depression circuitry is proposed to mediate/contribute to the greatly reduced antidepressant action of monoamine-based antidepressants in GPR39KO mice. |
