Wilma V. Richiez Mateo, Mario Lloret, Pedro Bonilla-Rullan, Roxsana Ayala-Pagán, Leslievette Hernández Román,

and Jennifer L. Barreto Estrada, PhD

Substance use disorders (SUD) are cognitive disorders of chronic relapse in which an organism develops a dependency to a substance. Although it is not fully understood, studies suggest that neuroplasticity changes on the neural circuits of the mesolimbic dopaminergic system are key players for the lack of extinction of persistent drug-seeking behavior. Previously, we showed that male rats that were able to extinguish drug-seeking behavior after being subjected to morphineinduced conditioned placed preference (CPP) exhibited higher levels of brain derived neurotrophic factor (BDNF) in the hippocampus and the amygdala. Also, male rats in the extinction group showed less frequency of rearings as a measure of withdrawal-like symptoms, as compared to animals in the sham-extinction group (absence of extinction training). Frequency of rearings in the extinction and extinction-resistant groups were similar. However, research on whether female rats show similar results at both the behavioral and molecular level has not been previously done.

Therefore, this investigation will determine in females and will compare to males: 1) morphine conditioning and extinction, 2) frequency of rearings, and 3) the expression of BDNF in the mesolimbic dopaminergic system. Preliminary results show similar conditioning patterns between male and female rats, whereas females spend less time in the drug-paired side during the extinction test day in comparison to males. Interestingly, twenty-five (25) percent of female rats were able to extinguish their morphine CPP, as compared to fifty (50) percent in males. Frequency of rearings in females were less in animals in the extinction group than in the extinction-resistant.

We also showed mature BDNF (14 kDa) expression in the hippocampus of female rats, and further studies will be performed to determine the correlation between extinction and BDNF as compared to males. Our study focuses on understanding the underlying biological mechanisms of opioid addiction, given the recent opioid crisis in the United States. Therefore, by understanding addiction, we are directly working towards surpassing this public health crisis.

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