Structural plasticity of the mesolimbic system associated with female sexual reward.

Abstract

Female sexual experience is a well established model of naturally motivated behaviors, activating the mesolimbic dopamine circuit which results in dopamine release within the nucleus accumbens. Repeated exposure to sexual behavior, through dopamine release within the nucleus accumbens, will alter a number of behavioral and cellular endpoints. An unanswered question is whether structural plasticity within the nucleus accumbens accompanies these other changes following sexual experience, which would have significant implications on its function. Using a DiOlistic labeling approach, we visualized medium spiny neurons within the nucleus accumbens core, nucleus accumbens shell and caudate-putamen, and determined that repeated sexual experience significantly increased spine density of medium spiny neurons specifically within the nucleus accumbens core. Medium spiny neurons are generally segregated into one of two phenotypic populations, those that express dopamine D1 receptor expressing, and those that express dopamine D2 receptors. These two phenotypes have opposing functions on intracellular signaling. We found that increases in spine density of medium spiny neurons were limited to the dopamine D1 receptor expressing phenotype within the nucleus accumbens core. Although these structural changes were defined by a dopaminergic receptor phenotype, altereations to spine density and structure suggest changes to glutamatergic input on spine heads; therefore increased dendritic spine density could indicate increased glutamatergic input into medium spiny neurons of the nucleus accumbens core. Glutamatergic input is also modulated by dopamine signals via dopamine receptors located on the spine shaft and dendrite. We therefore investigated whether glutamatergic or dopaminergic innervation was altered as a result of repeated sexual experience using antibodies directed against the presynaptic markers, vesicular glutamate transporter and dopamine transporter. We found no significant differences in glutamatergic innervation following sexual experience, as indicated by vesicular glutamate staining, and significant increases in dopamine transporter expression that were isolated to the caudal portion of the nucleus accumbens core. Together, these data provide further evidence that sexual behavior can induce persistent structural changes within the mesolimbic circuit that have the capacity to impact the overall function and may play a role in the coincident behavioral and cellular plasticity that is observed.