MK-329 blocks the inhibition of alcohol intake by CCK-8.
Peripheral administration of sulfated cholecystokinin octapeptide (CCK-8) potently reduces alcohol intake, preference, and blood levels in rats. MK-329 (L-364,718 or Devazepide) acts at peripheral cholecystokinin (CCKA) receptors to antagonize CCK-8's physiological and behavioral effects, such as pancreatic stimulation and inhibition of feeding. We determined whether CCKA receptor blockade would also prevent CCK-8's alcohol satiety effect. Water-deprived female and male rats (n = 7 for each) received randomized combinations of intraperitoneal injections of MK-329 (0, 100, 200, or 400 micrograms/kg) followed by CCK-8 (0 or 4 micrograms/kg). Rats were then given access to 5% w/v ethanol for 30 min, followed by 30-min access to water, with food ad lib. MK-329 at all doses significantly (p < 0.05) reduced the suppression of alcohol intake and food intake by CCK-8. MK-329 alone increased alcohol intake at 400 micrograms/kg, and increased food intake, in females and males at 100 and 200 micrograms/kg, respectively. We concluded that CCK-8's alcohol and food satiation effects depend on specific, peripheral CCKA receptors, and satiation of alcohol consumption and drinking-associated feeding reflect an endogenous functional interaction of CCK-8 with CCKA receptors.
Carr
B A
BA
Department of Psychology, University of Southern Colorado, Pueblo 81001-4901.
Ballou
J D
JD
Snell
J C
JC
Kulkosky
P J
PJ
D000428:Alcohol Drinking / Q000188:drug therapy*; D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology*; D020109:Devazepide; D005247:Feeding Behavior / Q000187:drug effects; D005260:Female; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012527:Satiation / Q000187:drug effects*; D012844:Sincalide / Q000037:antagonists & inhibitors*; D014868:Water Deprivation
D001570:Benzodiazepinones; D020109:Devazepide; D012844:Sincalide