Neurotensin modulates K +-stimulated dopamine release from the caudate-putamen but not the nucleus accumbens of mice with differential sensitivity to ethanol

Abstract

Slices of caudate-putamen (CP) and nucleus accumbens (NA) prepared from Long-Sleep (LS) and Short-Sleep (SS) mice were used to determine the effects of neurotensin (NT) and ethanol on K +-stimulated 3H-dopamine ( 3H-DA) release and to test the hypothesis that ethanol acts, in part, via NT receptor-mediated processes. Slices prepared from either LS or SS CP or NA did not differ in submaximal (25 mM) K +-stimulated 3H-DA release but 60 mM K + induced significantly greater 3H-DA release from LS CP slices compared with SS CP slices. NT had no effect on unstimulated 3H-DA overflow but enhanced 25 mM K +-stimulated 3H-DA release from slices of the CP of both lines of mice. Augmentation of DA release by NT from caudate slices was concentration dependent and tetrodotoxin (TTX) insensitive, implicating a role of presynaptic neurotensin receptors located on nigrostriatal DA neurones. In contrast, NT did not enhance K +-stimulated 3H-DA release from NA slices from either line of mice. The absence of an NT effect in NA slices was not due to a rapid desensitization of NT receptors but the data were consistent with the absence of presynaptic NT receptors on dopaminergic terminals in the NA. Between-line differences were observed in the effect of ethanol on NT enhancement of 25 mM K +-stimulated 3H-DA release from CP slices. Ethanol (100 mM) applied concomitantly with NT blocked the NT enhancement of 3H-DA release from CP slices of LS but not SS mice. In contrast, this concentration of ethanol, in the absence of NT, had no effect on 25 mM K +-stimulated 3H-DA release. Differences in the ethanol interaction with NT receptor-mediated processes may account, in part, for genetic differences in ethanol sensitivity.