Antidepressant-Like Effect of the Norepinephrine-Dopamine Reuptake Inhibitor Bupropion in a Mouse Model of Huntington's Disease with Dopaminergic Dysfunction.

BACKGROUND

The pre-motor stages of Huntington's disease (HD) are commonly associated with psychiatric manifestations including depression. Recent clinical data indicate that dopaminergic dysfunction is common in both symptomatic and pre-manifest HD gene carriers. There is also increasing evidence implicating catecholamine dysfunction in the pathophysiology of depression.

OBJECTIVE

In this study, we aimed to functionally investigate the dopaminergic system in the R6/1 mouse model of HD prior to onset of motor symptoms.

METHODS

We assessed the effects of acute administration of bupropion (a dopamine-norepinephrine reuptake inhibitor) on spontaneous locomotor activity and depression-like behaviour (using the forced-swim test).

RESULTS

Here we show that the bupropion-induced increased locomotor activity found in wild-type animals was no longer observed in HD mice. We also found that acute administration with bupropion rescued depressive-like behaviours in HD animals, possibly through dopamine D2/D3 receptor mechanisms.

CONCLUSION

Our present data are the first in vivo evidence of an impaired dopamine D1 receptor-dependent function in pre-motor symptomatic R6/1 HD mice. Moreover, our findings suggest clinical potential for bupropion to alleviate depressive symptoms in HD.