title: Ventral Midbrain NTS1 Receptors Mediate Conditioned Reward Induced by the Neurotensin Analog, D-Tyr[11]neurotensin.
abstract: The present study was aimed at characterizing the mechanisms by which neurotensin (NT) is acting within the ventral midbrain to induce a psychostimulant-like effect. In a first experiment, we determine which subtype(s) of NT receptors is/are involved in the reward-inducing effect of ventral midbrain microinjection of NT using the conditioned place-preference (CPP) paradigm. In a second study, we used in vitro patch clamp recording technique to characterize the NT receptor subtype(s) involved in the modulation of glutamatergic neurotransmission (excitatory post-synaptic current, EPSC) in ventral tegmental neurons that expressed ([Formula: see text]), or do not express ([Formula: see text]), a hyperpolarization-activated cationic current. Behavioral studies were performed with adult male Long-Evans rats while electrophysiological recordings were obtained from brain slices of rat pups aged between 14 and 21 days. Results show that bilateral ventral midbrain microinjections of 1.5 and 3 nmol of D-Tyr[(11)]NT induced a CPP that was respectively attenuated or blocked by co-injection with 1.2 nmol of the NTS1/NTS2 antagonist, SR142948, and the preferred NTS1 antagonist, SR48692. In electrophysiological experiments, D-Tyr[(11)]NT (0.01-0.5 μM) attenuated glutamatergic EPSC in [Formula: see text] but enhanced it in [Formula: see text] neurons. The attenuation effect ([Formula: see text] neurons) was blocked by SR142948 (0.1 μM) while the enhancement effect ([Formula: see text] neurons) was blocked by both antagonists (0.1 μM). These findings suggest that (i) NT is acting on ventral midbrain NTS1 receptors to induce a rewarding effect and (ii) that this psychostimulant-like effect could be due to a direct action of NT on dopamine neurons and/or an enhancement of glutamatergic inputs to non-dopamine ([Formula: see text]) neurons.
authors.affiliation: Department of Neurosciences, Université de MontréalMontréal, QC, Canada; FRQ-S Research Group in Behavioral Neurobiology, Department of Psychology, Concordia UniversityMontréal, QC, Canada.
authors.forename: Khalil
authors.initials: K
authors.lastname: Rouibi
authors.affiliation: Department of Psychiatry, Faculty of Medicine, Université de Montréal Montréal, QC, Canada.
authors.forename: Poulomee
authors.initials: P
authors.lastname: Bose
authors.affiliation: Department of Neurosciences, Université de MontréalMontréal, QC, Canada; FRQ-S Research Group in Behavioral Neurobiology, Department of Psychology, Concordia UniversityMontréal, QC, Canada.
authors.forename: Pierre-Paul
authors.initials: PP
authors.lastname: Rompré
authors.affiliation: Department of Psychiatry, Faculty of Medicine, Université de Montréal Montréal, QC, Canada.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Warren
keywords: conditioned reward; glutamate; neurotensin; ventral midbrain