Elsevier

Peptides

Volume 4, Issue 6, November–December 1983, Pages 955-961
Peptides

In vivo release of dopamine during perfusion of neurotensin in substantia nigra of the unrestrained rat

https://doi.org/10.1016/0196-9781(83)90095-5Get rights and content

Abstract

The functional effect of neurotensin on the kinetics of dopamine (DA) release in the substantia nigra of the freely moving rat was investigated. After guide tubes for push-pull perfusion were implanted stereotaxically just above the substantia nigra, endogenous stores of DA in this structure were labelled by micro-injection of 0.02–0.05 μCi of [14C]-DA. Then an artificial cerebrospinal fluid (CSF) was perfused within the site at a rate of 20 μl/min at successive 5 min intervals. Neurotensin added to the CSF perfusate in concentrations of 0.05–0.1 μg/μl evoked an immediate, Ca++ dependent release of DA from sites directly within the substantia nigra or a delayed efflux when the peptide was perfused at the edge of this structure. Neurotensin failed to affect the pattern of release of this monoamine at sites which were not within the substantia nigra. Further, the body temperature of the rat also was not altered by neurotensin at any of the sites of perfusions. A relatively inactive analogue of the peptide, [D-Arg]9 neurotensin, was essentially without effect on DA activity. In double isotope experiments in which the substantia nigra of the rat was labelled with both [3H]-5-HT and [14C]-DA, the perfusion with neurotensin failed to affect 5-HT efflux while the release of DA was enhanced. Chromatographic analysis of the metabolites of DA in samples of push-pull perfusates revealed that neurotensin enhanced significantly the level of DOPAC and HVA. Overall, these results demonstrate that in the unrestrained rat neurotensin acts selectively within the substantia nigra to alter the presynaptic, Ca++ dependent release of DA. It is suggested that the mechanism by which the tri-decapeptide functions within this brainstem structure is through its modulation of nigral dopaminergic neurons.

References (36)

Cited by (37)

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    Citation Excerpt :

    The neuromodulatory effects of NT are specific for NT receptor activation, as these effects are not mimicked by either glutamate or choleycystokinin, both neurotransmitters that also increase DA cell firing (Shi and Bunney 1991b). Dopamine neurons in the VTA and SN display different thresholds for NT-induced depolarization (Seutin et al 1989; Shi and Bunney 1990) and depolarization inactivation (Shi and Bunney 1991a), with NT having a greater effect in the VTA than in the SN (Myers and Lee 1983; Pinnock and Woodruff 1994; Seutin et al 1989). This effect is similar to atypical antipsychotic drugs that exert relatively selective effects on the VTA.

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