Génesis Rodríguez-Torres¹, R. Morales-Silva¹, J. Pérez-Torres¹, Y. Pérez-Pérez¹,

M. Martínez-Vélez² , H. Manso-Skerett ¹, U. Gelpí-Dominguez ¹, and M. Sepúlveda-Orengo¹

1 Ponce Health Sciences University, Ponce Research Institute, Ponce, PR

2 Pennsylvania State University

Cocaine is a psychostimulant drug that acts primarily on the limbic system. One of the main problems in cocaine addiction is high incidence of relapse due to its strongly addictive effects.

Currently, there is no pharmacological intervention approved for the treatment of stimulants use disorders, including cocaine. However, several studies have shown that physical activity, such as exercise, can prolong drug abstinence and mitigate drug-seeking symptoms in humans. A reduction in drug seeking has also been shown in animal models, where several studies have shown that aerobic exercise increases glutamate transporter-1 (GLT-1) expression from the hippocampus, as well as the hippocampal glial fibrillary acidic protein (GFAP) expression. In addition, a decreased expression of aquaporin-4 (AQP4) reduced cocaine-induced locomotor activity and restored dopamine and glutamate levels in the nucleus Accumbens (NAc).

Nevertheless, it is still unknown how aerobic exercise reduces cocaine addiction development and regulates GLT-1, GFAP and AQP4 in an animal model. We hypothesized that aerobic exercise restores GLT-1, GFAP and AQP4 expression in the NAc and prefrontal cortex in rats with cocaine history correlating with reduced seeking behavior. To test our hypothesis, male rats were exposed to 12 sessions of short-access self-administration, followed by 16 sessions of extinction. After each session of extinction, rats were placed in boxes equipped with a running wheel for a period of 6 hours. Following the behavioral protocol, protein levels of GLT-1, GFAP and AQP4 were measured by western blots. Preliminary data shows male and female rats that performed aerobic exercise during extinction showed reduced cocaine- seeking behavior, compared with locked-wheels and home-caged groups. There are no differences between cocaine groups or saline groups in terms of active lever presses or infusions during self- administration. In addition, it appears that rats in the saline group run more than those in the cocaine group. Expression of astroglial proteins AQP4 and GFAP in NAc and PL seems to show no difference between groups, and no difference between groups was observed either in astroglial GLT-1 expression in the PL region. Our results replicate those of previous studies, confirming that rats exposed to cocaine had reduced GLT-1 expression in the NAc. However, according to our results aerobic exercise does not restore GLT-1 in the NAc to normal levels, suggesting that exercise may use another molecular mechanism to attenuate cocaine- seeking behavior.

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