NEUROCHEMICAL AND BEHAVIORAL-EFFECTS OF NEUROTENSIN VS [D-TYR(11)]NEUROTENSIN ON MESOLIMBIC DOPAMINERGIC FUNCTION

Microinjection of neurotensin(1-13) or neurotensin(1-13) into the vent ral tegmental area (VTA) of anaesthetized rats produced dose-dependent (1-100 pg) dopamine release in the nucleus accumbens as measured by d ifferential pulse amperometry (DPA). Higher doses (100 pg(-10) ng) of [D-Tyr(11)]neurotensin were required to produce an identical effect. I n addition, the 3 peptides enhanced the K+-evoked [H-3]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 cannulat ed rats produced contralateral circling. [D-Tyr(11)]neurotensin was ef fective in a dose-dependent manner, between 40 and 320 ng. Similar eff ects were observed with 80 ng of neurotensin(1-13) and neurotensin(8-1 3) in presence of the protease inhibitor thiorphan. In view of the hig her potency of neurotensin(1-13) and neurotensin(8-13) versus [D-Tyr(1 1)]neurotensin to stimulate DA release both in vivo and in vitro and t he higher efficacy of [D-Tyr(11)]neurotensin to induce circling, this study further strengthens the concept of neurotensin receptor heteroge neity.