Synaptic Sex Differences in the Nucleus Accumbens

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DESCRIPTION (provided by applicant): The neural circuitry of reward is an evolutionary conserved and adaptive mechanism which functions to reinforce the acquisition of essential resources, such as food and mates for species survival. Drugs of abuse hijack these same neural pathways, and continued use leads to addiction, the detriment of health and life quality, and in some cases, a permanent change in brain structures. Ample evidence exists for females to become addicted more quickly and have a greater propensity for relapse than males to drugs of abuse. However, no studies have addressed if pre-existing sexual dimorphisms exist in the structure of circuits underlying this behavior. The goal of this research is to investigate a potential neuroanatomical substrate for sex differences in addiction-related behaviors. I will quantify synaptic and neurochemical characteristics in the nucleus accumbens (NAc), an integral link in the neural circuitry of reward and addiction. My hypothesis is that NAc neurons in females not only receive greater excitatory input than males but also contain greater numbers of dopaminergic contacts in relation to excitatory inputs that may facilitate the action of dopamine during drug exposure. I will test this hypothesis by using light and electron microscopy to quantify numbers of excitatory synapses, glutamatergic input, and dopamine-positive varicosities containing or contacting excitatory synapses in male and female adult rats. While the major brain areas involved in drug addiction are well characterized, few studies have addressed why women are more prone to addiction than men. This research will provide new insights about the neural basis for sex differences in addictive behaviors.