Neurochemical and behavioural effects of neurotensin vs [D-Tyr 11]neurotensin on mesolimbic dopaminergic function

• Published in: Neuropeptides (Edinburgh) Vol. 28; no. 1; pp. 43 - 50
• Main Authors: Steinberg, R, Brun, P, Souilhac, J, Bougault, I, Leyris, R, Le Fur, G, Soubrié, DP
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 1995; Elsevier
• Subjects: Animals; Behavior, Animal; Biological and medical sciences; Central nervous system; Central neurotransmission. Neuromudulation. Pathways and receptors; Dopamine - metabolism; Dose-Response Relationship, Drug; Fundamental and applied biological sciences. Psychology; 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; Vertebrates: nervous system and sense organs; Dopamine; Rat; Brain stem; Rodentia; Central nervous system; Neurotensin; Catecholamine; Neuropeptide; Nucleus accumbens; Vertebrata; Mammalia; Ventral tegmental; Analog; Neurotransmitter; Brain (vertebrata)
• ISSN: 0143-4179; 1532-2785
• DOI: 10.1016/0143-4179(95)90073-X

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-Tyr
11neurotensin 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-Tyr
11]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-Tyr
11]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-Tyr
11]neurotensin to stimulate DA release both in vivo and in vitro and the higher efficacy of [D-Tyr
11]neurotensin to induce circling, this study further strengthens the concept of neurotensin receptor heterogeneity.