Thyrotropin releasing hormone analog TA-0910 suppresses alcohol intake in alcohol drinking African green monkeys.
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.
Rezvani
A H
AH
Skipper Bowles Center for Alcohol Studies, University of North Carolina School of Medicine at Chapel Hill, USA.
Garbutt
J C
JC
Overstreet
D H
DH
Li
L
L
Walker
C H
CH
Yang
Y
Y
Mason
G A
GA
D000428:Alcohol Drinking / Q000503:physiopathology*; D000818:Animals; D002522:Chlorocebus aethiops; D004326:Drinking / Q000187:drug effects / Q000502:physiology; D008297:Male; D009042:Motivation; D018377:Neurotransmitter Agents / Q000502:physiology; D018697:Nootropic Agents / Q000494:pharmacology*; D051381:Rats; D012439:Saccharin / Q000008:administration & dosage; D013045:Species Specificity; D013649:Taste / Q000187:drug effects / Q000502:physiology; D013973:Thyrotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology
D018377:Neurotransmitter Agents; D018697:Nootropic Agents; C065049:TA 0910; D013973:Thyrotropin-Releasing Hormone; D012439:Saccharin