This project proposes to continue the selective breeding program to develop high (HAS) and low (]LAS) alcohol sensitive rats. The animals have proven useful in elucidating the mechanism by which alcohol depresses the central nervous system. The project has replicated the classic selection for alcohol sensitivity in mice, the short- and long-sleep mice (SS and LS) with a much more closely controlled genetic protocol including replicate and control lines. Rats, originating from a large genetically heterogeneous base population, are selected to have either prolonged or shortened """"""""sleep times (i.e., duration of loss of the righting response) following a standard intraperitoneal dose of alcohol. Six lines, with two replicates in each direction, are maintained, two high sensitivity (HAS), two low sensitivity (LAS) and two control (CAS) lines. The relative effects of ethanol metabolism are assessed by measurement of blood alcohol levels upon recovery of the righting response. Within family selection is used and a minimum of ten families per line are maintained. Proposed new studies include back selection to check completeness of the selection, development of recombinant inbred animals, testing of correlated responses relating to acute tolerance, preference, reinforcement, activity, temperature, neurotensin functions, ganglioside levels, and response to other hypnotic agents.
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