EFFECT OF EXOGENOUS GM1 ON ETHANOL SENSITIVITY IN SELECTIVELY BRED MOUSE LINES

Ethanol sensitive long-sleep (LS) and ethanol resistant short-sleep (S S) mice are lines that have been genetically selected for differential central nervous system sensitivities to the hypnotic effect of ethano l. Because they were genetically selected only for differences in sens itivity to ethanol hypnosis, biochemical and physiological differences between them are likely related to their differential ethanol sensiti vity. The synaptosomal and whole brain concentration of GM1 gangliosid e was previously shown to differ significantly between the lines. Furt her, GM1 alters membrane responses to ethanol, including a differentia l effect on LS and SS synaptosomal membrane disordering. Therefore, GM 1 was administered intracerebroventricularly (icy) with micro-osmotic pumps, to partially bypass the blood-brain barrier and to test its eff ect on CNS sensitivity to ethanol hypnosis in LS and SS mice, In the f irst experiment, 3 days' infusion of GM1 (20 mu g/mu l, 24 mu l/day), saline control and treated LS and SS mice were tested for both regaini ng of the righting reflex and waking brain ethanol concentration. Inco rporation of H-3-GM1 into brain membranes was verified by scintillatio n spectroscopy, GM1 did not alter ethanol sensitivity or brain ethanol concentration at time of waiting in LS mice. Conversely, SS mice trea ted with GM1 were significantly more sensitive to ethanol hypnosis tha n saline controls as measured by the time to regain the righting refle x (''sleep time'') and waking brain ethanol concentrations. In the sec ond experiment, GM1-treated SS mice were again significantly more sens itive to ethanol hypnosis than saline controls, GM1 incorporation into the contralateral and ipsilateral cerebral hemispheres was determined by highperformance liquid chromatography.