Thyrotropin Releasing Hormone Analog TA-0910 Suppresses Alcohol Intake in Alcohol Drinking African Green Monkeys |
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Authors: | Amir H Rezvani James C Garbutt David H Overstreet Li Li Cheryl H Walker Y Yang George A Mason |
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Institution: | Skipper Bowles Center for Alcohol Studies (A.H.R., J.C.G., D.H.O., Y.Y., G.A.M.), Brain and Development Research Center (J.C.G., C.H.W., G.A.M.), and Department of Psychiatry (A.H.R., J.C.G., D.H.O., L.L., G.A.M.), The University of North Carolina School of Medicine at Chapel Hill, Chapel Hill, North Carolina. |
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Abstract: | In previous studies, we found that single injections of the thyrotropin-releasing hormone analog TA-0910 dose-dependently reduced alcohol intake and preference in alcohol-preferring (P) and Fawn-Hooded (FH) rats over a 24-hr period of continuous access to alcohol and water. However, several consecutive daily injections of TA-0910 resulted in the development of tolerance to these effects. In the present study, we found that in a 5-hr limited-access schedule in which monkeys could select an aqueous alcohol solution (7.5% v/v) or tap water, single doses of TA-0910 (0.0625, 0.125, 0.25, 0.5, and 0.75 mg/kg), similar to those found effective in P and FH rats, reduced consumption of alcohol. In this protocol, tolerance to the attenuating effects of TA-0910 on alcohol intake was not evident after five consecutive once-daily doses of 0.5 mg/kg. Furthermore, it was shown that a single dose of 0.75 mg/kg TA-0910 did not significantly influence 24-hr water intake when water was the only available fluid, but did reduce the intake of a preferred solution of saccharin. These findings suggest that activation of brain thyrotropin-releasing hormone systems reduces alcohol intake in primates and that tolerance to this effect is not evident within 5 days under a limited access schedule. |
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Keywords: | TRH Analog Vervet Monkeys Alcohol Intake Tolerance Drinking Behavior Saccharin |
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