CNS monoamine levels and the effect of DSP4 on ethanol sensitivity in LS and SS mice

Brain area monoamine levels were determined in selectively-bred ethanol sensitive (LS) and insensitive (SS) mice. Norepinephrine, dopamine and serotonin were measured using high performance liquid chromatography coupled with electrochemical detection. Brain regions studied included cerebellum, brain stem, striatum, frontal cortex, hippocampus and hypothalamus. LS and SS mice exhibited similar regional monamine levels with the exception of differences in brain stem and cerebellar norepinephrine levels. The role of norepinephrine in regulating ethanol sensitivity of these mice was investigated using the neurotoxin, DSP4 (selectively lesions central noradrenergic pathways). Treatment with DSP4 did not alter ethanol sensitivitiy in the LS or SS mice, measured by duration of righting response loss and blood ethanol concentration at its recovery. Differences in brain stem and cerebellar norepinephrine levels between the LS and SS mice were considerably smaller than the large decreases in levels produced in both lines by DSP4. It is concluded that although synaptically-released monoamines may influence ethanol responses, norepinephrine probably does not directly mediate differences in behavioral sensitivity to ethanol between these mouse lines.