ABSTRACT
Thyrotropin releasing hormone (TRH) has been reported to reduce stress- and deprivation-induced eating, hypothetically by induction of satiation. Early work demonstrated thyroid extracts reduced alcohol intake, and recent research shows a TRH analog specifically inhibits alcohol preference. We determined whether parenteral administration of TRH reduces alcohol consumption and choice in a manner consistent with a satiation effect. Water-restricted ad lib fed female and male rats (n = 12) were given access to 5% w/v ethanol 0 or 30 minutes after intraperitoneal (i.p.) injection of TRH. TRH (20-40 mg/kg) inhibited alcohol intake only if injected immediately before alcohol access. Inhibition of alcohol intake was reliably accompanied by increased production of fecal boli but not by reliably decreased food intake. Rats given a choice of 2% w/v ethanol and water decreased alcohol preference after TRH (20 mg/kg) but did not reduce total fluid intake. Results are partially consistent with the hypothesis of TRH as one of several functional elements in the integrative neuropeptide control of alcohol consumption via short-term satiation.
Subject(s)
Alcohol Drinking/drug therapy , Thyrotropin-Releasing Hormone/therapeutic use , Animals , Defecation/drug effects , Dose-Response Relationship, Drug , Female , Male , Rats , Rats, Wistar , Satiation/drug effects , Thyrotropin-Releasing Hormone/pharmacologyABSTRACT
Administration of the neuropeptide cholecystokinin (CCK) is known to reduce food and alcohol intake and preference. The food satiation effect of CCK is reportedly dependent on serotonergic neurotransmission. Administration of 8-OH-DPAT, a serotonin1A autoreceptor agonist, reduces the ability of CCK to inhibit feeding. We determined if CCK's alcohol satiation effect also depends on activity of serotonergic neurons by administering 8-OH-DPAT (120-240 microg/kg) to 23-h water-deprived female and male rats, followed 1 h later by i.p. injection of CCK (4 microg/kg) and 30-min access to 5% w/v ethanol. 8-OH-DPAT significantly (p < 0.05) interacted with CCK, and reduced CCK's ethanol satiation effect when given i.p. but increased CCK's effect when given s.c. Female rats showed this interaction of 8-OH-DPAT with CCK at a higher dose than males when given i.p., but females were more sensitive to s.c. 8-OH-DPAT's ability to reduce ethanol intake. Results are consistent with previous findings of dose-, sex-, and route-dependent biphasic effects of 8-OH-DPAT on feeding and ethanol intake. A partial dependence of CCK's alcohol satiation effect on serotonergic neurotransmission is revealed in this design.
