MESENCEPHALIC MICROINJECTIONS OF NEUROTENSIN-(1-13) AND ITS C-TERMINAL FRAGMENT, NEUROTENSIN-(8-13), POTENTIATE BRAIN-STIMULATION REWARD

Using the curve shift method, we assessed the effects of ventromedial mesencephalic tegmental (VMT) microinjections of an equimolar concentr ation of neurotensin-(1-13) (NT-(1-13)) and of its C-terminal fragment , neurotensin-(8-13) (NT-(8-13)), on operant responding for rewarding electrical stimulation of the caudal mesencephalic central gray. The e ffects of NT-(1-13) and NT-(8-13) on brain stimulation reward (BSR) we re also compared to those of systemically administered quinpirole (0.1 and 0.2 mg/kg, s1.c.), a direct dopamine agonist, and GBR-12909 (10 a nd 20 mg/kg, i.p.), a selective dopamine uptake blocker. At the concen tration injected, NT-(8-13) was as effective as NT-(1-13) at facilitat ing BSR, producing significant leftward shifts of the function relatin g the rate of responding to the stimulation frequency (R/F function); neither form of the peptide was effective when injected in regions dor sal to the VMT. Similarly, GBR-12909 produced a parallel leftward shif t of the R / F function, but, unlike NT-(1-13), also significantly inc reased the asymptotic rates of responding. In contrast, the high dose of quinpirole produced non-parallel leftward shifts of the R / F funct ion and suppressed the asymptote. The similarity between the effects o f neurotensin and GBR-12909 on one hand, and the differences between t hose of neurotensin and quinpirole on the other, suggest that activati on VMT neurotensin receptors potentiate BSR by enhancing increases in dopamine neurotransmission that are contingent upon operant responding or rewarding brain stimulation, or both. Moreover, the comparable eff ectiveness of NT-(1-13) and NT-(8-13) suggests that the observed facil itation of BSR is mediated by activation of physiologically-relevant V MT neurotensin receptors.