Intravenous self-administration of ethanol in beta-endorphin-deficient mice.
Extensive research on both human alcoholics and in animal models of alcoholism has implicated the release of endogenous opioids in the consumption of ethanol. Various experiments using opioid antagonists have indicated that these drugs cause both humans and animals to decrease their consumption of ethanol. However, it remains unclear exactly which of the endogenous opioids mediates the rewarding effects of ethanol. The present experiment used intravenous self-administration of ethanol to determine whether beta-endorphin (BE)-deficient mice differed from wild-type (WT) mice in ethanol self-administration. The BE-deficient mice completely lack BE, but are otherwise similar to the WT mice. By using intravenous self-administration, we were able to rule out any ability of BE to mediate differences in ethanol consumption via palatability factors alone. Both types of mice were 7 generations backcrossed onto a C57BL/6J inbred strain background. During nine daily, 2-hr free-operant sessions, 14 BE-deficient and 17 WT mice could nosepoke for 75 mg/kg ethanol infusions delivered intravenously on an fixed-ratio 3 schedule with a 2-sec time-out after each reinforcer delivery. Reinforcer delivery occurred following nosepokes in only one of two holes. Contrary to what was expected, BE-deficient mice acquired selective operant responding for ethanol, whereas WT mice did not. Although the two genotypes did not differ in either operant or locomotor behavior during the first session, by the end of the nine sessions, BE deficient mice were reliably nosepoking for ethanol, whereas WT mice were not. These findings may indicate that BE is not essential for the postingestive reinforcing effects of ethanol in these animals.
Grahame
N J
NJ
Department of Behavioral Neuroscience, Oregon Health Sciences University, Portland, USA.
Low
M J
MJ
Cunningham
C L
CL
D000437:Alcoholism / Q000235:genetics / Q000503:physiopathology*; D000818:Animals; D003216:Conditioning, Operant / Q000502:physiology; D000431:Ethanol / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009043:Motor Activity / Q000187:drug effects; D012055:Reinforcement Schedule; D012646:Self Administration; D001615:beta-Endorphin / Q000172:deficiency* / Q000235:genetics / Q000502:physiology
D000431:Ethanol; D001615:beta-Endorphin