CRF1 Receptor Antagonist Injections Increase Medial Prefrontal Cortex Serotonin after Alcohol Self-Administration
Carlson, Julia M.
- Aggressive behaviors comorbid with alcohol abuse are a public health crisis. These behaviors are historically correlated to an inverse concentration of serotonin in the central nervous system. Corticotropin-Releasing Factor (CRF) antagonists that mediate the physiological stress response have recently begun to be developed to treat alcohol abuse. As CRF modulates serotonergic release, it may affect ... read moreaggressive behaviors. A previous behavioral study in our lab found that the CRF1 antagonist CP-154,526 attenuated alcohol-heightened aggression in Carworth Farms Webster (CFW) mice. Based on this experiment, we decided to use in vivo microdialysis to evaluate the change in serotonin concentration in the medial prefrontal cortex following ethanol self-administration, CP-154,526 injection (17 mg/kg intraperitoneal and 0.6 ?g microinjection into the dorsal raphe nucleus), and paired self-administration and acute drug injection. 1 g/kg ethanol self-administered was seen to significantly increase serotonin concentration. CP-154,526 i.p. administered had no overall effect, but trended towards increasing serotonin concentration. Acute injections following self-administration increased serotonin concentration, but the microinjection was only compared to its baseline as opposed to an inert vehicle injection. Overall, serotonin concentration increases following acute injection CP-154,526 and ethanol self-administration correlate to the anti-aggressive effects observed in the previous behavioral study. CP-154,526 may be a useful therapeutic in treating alcohol abuse comorbid with aggressive behaviors.read less