CHARACTERIZATION OF NEUROTENSIN-STIMULATED PHOSPHOINOSITIDE HYDROLYSIS IN BRAIN-REGIONS OF LONG-SLEEP AND SHORT-SLEEP MICE

Previous studies have shown that long sleep (LS) and short sleep (SS) mice, which were selectively bred for differences in brain sensitivity to ethanol, differ in neurotensin (NT) receptor densities in specific brain regions. The present study was designed to determine whether th ese receptor differences mediate differences in the effects of NT on t he phosphoinositide (PI) second messenger system in four brain regions from LS and SS mice. Baseline and NT- or carbachol-stimulated PI hydr olysis were Ca2+-dependent. Stimulation of PI hydrolysis by NT or carb achol was region specific; NT effect was approximately equal in ventra l midbrain (VMB) and entorhinal cortex (EC) with slightly less stimula tion in nucleus accumbens (NA) and no effect in the cerebellum (CE). C arbachol-enhanced PI hydrolysis was greatest in the VMB followed by EC and NA with no stimulation in the CE. There were no between line (LS vs. SS) differences in carbachol effects, but stimulation by NT was gr eater in EC and NA from LS than from SS mice. Ethanol enhanced NT-stim ulated, but not carbachol-stimulated, PI metabolism in SS and LS NA br ain slices. Results with levocabastine, an inhibitor of low-affinity N T receptor (NT(L)) binding, suggest that NT may stimulate PI hydrolysi s via NT(L), as well as high-affinity receptors.