Targeting Substantia Nigra through Oxytocin Receptors.

TARGETING SUBSTANTIA NIGRA THROUGH OXYTOCIN RECEPTORS. The paraventricular nucleus of the hypothalamus (PVN) contains parvocellular oxytocinergic neurons projecting to extrahypothalamic brain areas such as the hippocampus, amygdala, ventral tegmental area (VTA) and substantia nigra (SN). Some oxytocin functions in any of these areas have already been identified whereas the role of oxytocinergic projections to the SN and the nature of the interaction between oxytocin and the nigral dopaminergic neurons involved in the voluntary control of movement are still unclear. The aim of this study was to investigate the effect, on the dopaminergic nigrostriatal function, of the injection into the SN of a novel cytotoxin that selectively targets and destroys cells expressing oxytocin receptors. Male Sprague Dawley rats (n=24) were monolaterally or bilaterally injected into the SN with the toxin or vehicle (PBS). Locomotor activity was assessed before and two and four weeks after injection using a Digiscan Activity Analyser. Immunohistochemistry was used to verify the presence and extent of the lesion in the dopaminergic neurons and to investigate any modifications in the GABAergic and the glutamatergic systems. After four weeks, animals bilaterally injected with the toxin showed a significant increase in locomotor activity (60%), not observed in monolaterally injected animals, whereas PBS injection had no effect. In toxin injected animals, Tyrosine Hydroxylase immunoreactivity was reduced in SN compacta somas and in their dendrites coursing into the pars reticulata while no evident variation in Glutamate Decarboxylase immunoreactivity was observed. Interestingly, preliminary results showed a tendency towards reduction in SN Vesicular Glutamate Transporters (VGluT1, VGluT2 and VGluT3) immunoreactivity, possibly correlated with the dopaminergic lesion extent, suggesting the potential induction of alterations also in the glutamatergic system. In conclusion, the increase in locomotor activity observed despite the dopaminergic degeneration suggests that oxytocin function in SN might involve other neuronal systems in addition to the dopaminergic one.