Inhibition of androgenic pathway impairs encoding of cerebellar-dependent motor learning in male rats

Cerebellar-dependent learning is essential for the adaptation of motor and no motor behaviors to changing contexts, and neuroactive steroids-mainly referred to as estrogens-may regulate this process. However, the role of androgens in this process has not been established, although they may affect cerebellar physiology. Thus, this study aims to determine whether the activation of androgenic neural pathways may take part in controlling the vestibuloocular (VOR) and optokinetic reflexes (OKR), which depend on a defined cerebellar circuitry. To answer this question, we acutely blocked the activation of androgen receptors (Ars) using systemic administration of the Ars antagonist flutamide (FLUT; 20 mg/Kg) in peripubertal male rats. Then, we evaluated the FLUT effect on general oculomotor performance in the VOR and OKR as well as VOR adaptive gain increases and decreases. We used a paradigm causing fast VOR adaptation that combined in phase/out phase visuo-vestibular stimulations. We found that FLUT impaired the gain increase and decrease in VOR adaptation. However, FLUT altered neither acute nor overtime basal ocular-motor performance in the VOR or OKR. These findings indicate that the activation of androgenic neural pathways participates in phenomena leading to fast VOR adaptation, probably through the modulation of plasticity mechanisms that underlie adaptation of this reflex. Conversely, androgens may not be essential for neural information processing demands in basal ocular-motor reflexes. Moreover, our results suggest that androgens, possibly testosterone and dihydrotestosterone, could rapidly regulate motor memory encoding in the VOR adaptation, acting at both cerebellar and extracerebellar plasticity sites.