Interaction between alcohol deprivation and morphine withdrawal in mice

Hybrid mice having had 12 weeks free access to flavored alcohol were deprived of it for 3 days. The increase in alcohol intake rate during first 1.5 h of renewal access as compared with its intake rate during the remaining 22.5 h (alcohol-deprivation effect, ADE) was used to select individuals having (HD) or lacking (LD) the ADE. The mice received morphine or placebo pellet implantation for 4 days followed by removal of alcohol and pellets. Cross-maze, acoustic startle response, and tail flick tests were conducted 1 day after morphine withdrawal and after 2 days of alcohol deprivation. Next day, during a second ADE test, placebo-treated HDs again showed ADE and LDs showed no ADE; the HDs during morphine withdrawal also still showed an ADE similar to those in placebo HDs, but LDs after morphine removal differed in showing an ADE. Significantly more hyperalgesia in HD than LD mice was observed during morphine withdrawal. Placebo HDs differed from placebo LDs in showing stereotyped behavior and kindling-like rise in acoustic startle response. Morphine withdrawal caused body weight loss, and converted the startle response curve in both LD and HD mice to a bell-shape curve. In HD mice the alcohol deprivation behavioral pattern was substituted by the corresponding morphine withdrawal pattern. The existence of distinct neural circuits responsible for the development of alcohol and morphine dependence is proposed.