Cocaine Self-Administration Differentially Modulates the Content of Cholesterol, Progesterone, and Testosterone in the Brain and Plasma of Male Rats.

Introduction: Chronic cocaine exposure results in changes in circulating steroid hormones, which is known to be associated with cocaine-seeking and cocaine-taking behavior. However, whether cocaine also alters the brain content of these steroid hormones and cholesterol, a precursor to all steroid hormones, has yet to be extensively investigated. Thus, the goal of this study was to determine whether cocaine self-administration (SA) altered the content of cholesterol and steroid hormones (progesterone and testosterone) in both the plasma and the brain of animals.

Methods: Male Sprague-Dawley rats were allowed to self-administer cocaine (1.5 mg/kg/infusion) for a maximum of 40 injections within 6 h per day for 5 consecutive days followed by cue reactivity test and cocaine SA under the progressive ratio schedule as a measure of motivation to acquire cocaine. Eighteen hours after the last behavior test, the blood and brain tissue, including the prefrontal cortex (PFC) and dorsal striatum (CPu), were collected for biochemical assays.

Results: While cocaine SA did not alter the content of cholesterol and progesterone in the plasma, it reduced cholesterol content and almost completely abolished progesterone content in both the PFC and CPu. Further, testosterone levels were reduced in the CPu and plasma. Notably, plasma testosterone was positively correlated with its content in the PFC and CPu.

Conclusions: Cholesterol and progesterone in the brain are more sensitive to changes induced by cocaine SA than those in the plasma. Future studies should focus on understanding the functional consequence of altered brain steroids on neurotransmission and cocaine-seeking and cocaine-taking behavior.