Ethanol-induced inhibition of norepinephrine release from brain slices obtained from LS and SS mice.

The effects of ethanol or prostaglandin E2 (PGE2) on K+-ion-stimulated or spontaneous (3H)-norepinephrine release were assessed in slices prepared from cortex and cerebellum of long-sleep (LS) and short-sleep (SS) mice. These lines were selectively bred for differences in ethanol-induced sleep time. Ethanol inhibited K+-stimulated release from LS cortical slices at lower concentrations than that required to inhibit release from SS cortical slices. Spontaneous release, on the other hand, was enhanced at lower ethanol concentrations in SS cortical slices. Ethanol inhibited K+-stimulated release equally in LS and SS cerebellar slices. Similarly, ethanol increased spontaneous release equally in LS and SS cerebellar slices. Thus, genotype and brain region influence the effect of ethanol on norepinephrine release. Since PGE2 has been reported to inhibit norepinephrine release, the effect of PGE2 on K+-stimulated norepinephrine release was examined in LS and SS cortical slices. PGE2 inhibited norepinephrine release equally in the two mouse lines. These data indicate that ethanol may elicit some of its depressant effects by altering norepinephrine release. The difference between the lines in inhibition of release probably does not involve differences in sensitivity to PGE2. Differences in ethanol-induced PGE2 production could, however, explain the differences in sensitivity of LS and SS cortical slices to ethanol-induced inhibition of K+-stimulated norepinephrine release.