Neurochemical and behavioural effects of neurotensin vs [D-Tyr11]neurotensin on mesolimbic dopaminergic function

Neuropeptides. 1995 Jan;28(1):43-50. doi: 10.1016/0143-4179(95)90073-x.

Abstract

Microinjection of neurotensin(1-13) or neurotensin(8-13) into the ventral tegmental area (VTA) of anaesthetized rats produced dose-dependent (1-100 pg) dopamine release in the nucleus accumbens as measured by differential pulse amperometry (DPA). Higher doses (100 pg-10 ng) of [D-Tyr11]neurotensin were required to produce an identical effect. In addition, the 3 peptides enhanced the K(+)-evoked [3H]DA release from nucleus accumbens slices. The stimulatory actions produced by 10(-8) M neurotensin(1-13) and neurotensin(8-13) were respectively of 96% and 72% while the effect of [D-Tyr11]neurotensin was only of 79% at 10(-6) M. Unilateral application of the 3 peptides in the VTA of cannulated rats produced contralateral circling. [D-Tyr11]neurotensin was effective in a dose-dependent manner, between 40 and 320 ng. Similar effects were observed with 80 ng of neurotensin(1-13) and neurotensin(8-13) in presence of the protease inhibitor thiorphan. In view of the higher potency of neurotensin(1-13) and neurotensin(8-13) versus [D-Tyr11]neurotensin to stimulate DA release both in vivo and in vitro and the higher efficacy of [D-Tyr11]neurotensin to induce circling, this study further strengthens the concept of neurotensin receptor heterogeneity.

MeSH terms

  • Animals
  • Behavior, Animal
  • Dopamine / metabolism*
  • Dose-Response Relationship, Drug
  • Male
  • Neurotensin / analogs & derivatives
  • Neurotensin / pharmacology
  • Nucleus Accumbens / drug effects
  • Nucleus Accumbens / metabolism*
  • Peptide Fragments / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Stereoisomerism
  • Ventral Tegmental Area / drug effects
  • Ventral Tegmental Area / metabolism*

Substances

  • Peptide Fragments
  • Neurotensin
  • neurotensin (8-13)
  • neurotensin, Tyr(11)-
  • Dopamine