Neurotensin modulates K(+)-stimulated dopamine release from the caudate-putamen but not the nucleus accumbens of mice with differential sensitivity to ethanol.
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.(ABSTRACT TRUNCATED AT 250 WORDS)
Duncan
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CC
Alcohol Research Center, School of Pharmacy, University of Colorado, Boulder 80309-0297.
Erwin
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VG
D000818:Animals; D002421:Caudate Nucleus / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D000431:Ethanol / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D009496:Neurotensin / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D011188:Potassium / Q000494:pharmacology*; D011699:Putamen / Q000187:drug effects / Q000378:metabolism*; D012890:Sleep
D009496:Neurotensin; D000431:Ethanol; D011188:Potassium; D004298:Dopamine