Effects of CRF-R1 and Opioid Antagonism on Alcohol Intake in C57BL/6J Mice
Kayyali, Tala M.
- Modulation of corticotropin-releasing factor (CRF) neural pathways and the opioid system has been promising for reducing ethanol intake in alcohol-dependent rodents and humans. Specifically, CRF receptor 1 (CRF-R1) antagonism in brain sites such as the dorsal raphÃ© nucleus (DRN) has been suggested to alter output involved in alcohol drinking. Naltrexone, an opioid antagonist, is a drug that is ... read morecurrently being used in the treatment of alcoholism. This research explores the role of antagonism of CRF-R1 and the opiate system in the DRN as they affect ethanol consumption in C57BL/6J mice. In a series of experiments, animals were given intermittent access to alcohol. After establishing stable drinking levels, mice received systemic injections of naltrexone (0.1, 1.0, 10.0 mg/kg) and then were implanted with guide cannulae into the DRN. Different doses of a CRF-R1 antagonist and naltrexone were infused intra-DRN to test for a reduction of alcohol consumption. Measures of withdrawal and blood ethanol concentration were taken to verify the alcoholism model in mice. Another batch underwent surgery after achieving stable drinking levels, then received intra-DRN infusions using different doses of CP-154,526, naltrexone, or a combination. Current findings indicate that both CP 154,526 and naltrexone are effective in significantly reducing ethanol intake, but do not affect water intake. The combination of both did not show an additive effect, but it did result in a greater reduction in ethanol intake than each drug had individually. This could mean that CRF and opioid receptors work independently on serotonin in the DRN. Future studies could investigate other areas where CRF and opioid receptors are co-localized such as the central amygdala or the locus coeruleus.read less