Amphetamine produces sex- and subregion-selective neuroplasticity in the amygdala of Wistar rats

Use of addictive drugs is partially sex-specific, with females to a larger extent reporting drug use as a coping strategy. Considering the key role for the amygdala in emotional processing, we hypothesized that part of these sex-differences could be attributed to drug-induced neuroplasticity in subregions of the amygdala. To test this hypothesis, female and male Wistar rats received amphetamine (2.0 mg/kg) once daily for 5 consecutive days. Following a two-week long drug free period whole cell electrophysiological recordings were conducted in the basolateral amygdala (BLA) and the central nucleus of the amygdala (CeA). In addition, given the impact of amphetamine use on the immune system, hematological analysis was performed to assess if the treatment paradigm would be sufficient to induce leukocytosis. Data demonstrate that amphetamine produces sex- and subregion-specific neuroplasticity, with reduced frequency of synaptic inputs and increased intrinsic excitability of BLA neurons from male rats, while decreased intrinsic excitability was observed in female rats. Neurophysiological characteristics were not significantly altered in CeA neurons of male rats exposed to amphetamine, but female rats demonstrated reduced cell capacitance and facilitated excitability. Hematological analysis revealed leukocytosis in both female and male rats exposed to amphetamine, with increased number of lymphocytes and monocytes. In conclusion, this study demonstrates that five days of amphetamine exposure is sufficient to produce sustained neurophysiological transformations in the amygdala and to activate the innate immune system. Outlined transformations are partially sex specific and could be important neurobiological underpinnings contributing to amphetamine dependence.