The subchronic effects of the TRH analog TA-0910 and bromocriptine on alcohol preference in alcohol-preferring rats: development of tolerance and cross-tolerance.
In a previous study, we showed that a single injection of the thyrotropin-releasing hormone analog TA-0910 dose-dependently reduced alcohol intake in alcohol-preferring (P) rats and increased their water intake over a 24-hr period. In the present study, the effects of seven consecutive, once-daily injections of TA-0910 (0.75 mg/kg, ip) on alcohol preference were determined. P rats developed tolerance to the attenuating effects of TA-0910 on alcohol intake within 3-5 days. Following the development of tolerance to TA-0910, rats were injected with the dopamine agonist bromocriptine (0.5 mg/kg, sc). In the presence of tolerance to TA-0910, the attenuating effect of bromocriptine on alcohol intake was reduced. When rats were made tolerant to the attenuating effects of bromocriptine, they exhibited tolerance to the attenuating effects of TA-0910. These findings indicate that tolerance to the effects of TA-0910 on alcohol intake occurs and suggest dopamine involvement in the mechanism of action of TA-0910 in reducing alcohol intake in P rats.
Skipper Bowles Center for Alcohol Studies, University of North Carolina School of Medicine, Chapel Hill 27599-7160.
G A
GA
Mason
A H
AH
Rezvani
D R
DR
Grady
J C
JC
Garbutt
D000428:Alcohol Drinking / Q000503:physiopathology*; D000437:Alcoholism / Q000503:physiopathology*; D000818:Animals; D001971:Bromocriptine / Q000494:pharmacology*; D004298:Dopamine / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D007279:Injections, Subcutaneous; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013973:Thyrotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000502:physiology
C065049:TA 0910; D001971:Bromocriptine; D013973:Thyrotropin-Releasing Hormone; D004298:Dopamine