Absence of Testes at Puberty Impacts Functional Development of Nigrostriatal But Not Mesoaccumbal Dopamine Terminals in a Wild-Derived Mouse

The nigrostriatal and mesoaccumbal dopamine systems are thought to contribute to changes in behavior and learning during adolescence, yet it is unclear how the rise in gonadal hormones at puberty impacts the function of these systems. We studied the impact of prepubertal gonadectomy (GDX) on later evoked dopamine release in male <i>Mus spicilegus</i>, a mouse whose adolescent life history has been carefully characterized in the wild and laboratory. To examine how puberty impacts dopamine neuron function in <i>M. spicilegus</i> males, we removed the gonads prepubertally at postnatal day (P)25 and then examined evoked dopamine release in the dorsomedial, dorsolateral (DLS), and nucleus accumbens core regions of striatal slices at P60-70 (late adolescence/early adulthood). To measure dopamine release, we used near-infrared catecholamine nanosensors which enable study of spatial distribution of dopamine release. We found that prepubertal GDX led to a significantly reduced density of dopamine release sites and reduced dopamine release at each site in the DLS nigrostriatal system compared with sham controls. In contrast, mesoaccumbal dopamine release was comparable between sham and gonadectomized groups. Our data suggest that during adolescence, the development of the nigrostriatal dopamine system is significantly affected by the rise in gonadal hormones in males, while the mesoaccumbal system shows no detectable sensitivity at this time point. These data are consistent with molecular studies in rodents that suggest nigrostriatal neurons are sensitive to androgens at puberty and extend our understanding of how gonadal hormones could impact the spatial distribution and release potential of dopamine terminals in the striatum.