AUTHOR=Rouibi Khalil , Bose Poulomee , Rompré Pierre-Paul , Warren Richard A. 

TITLE=Ventral Midbrain NTS1 Receptors Mediate Conditioned Reward Induced by the Neurotensin Analog, D-Tyr[11]neurotensin

JOURNAL=Frontiers in Neuroscience

VOLUME=9

YEAR=2015

URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2015.00470

DOI=10.3389/fnins.2015.00470

ISSN=1662-453X

ABSTRACT=<p>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 <italic>in vitro</italic> 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 (<inline-formula><mml:math id="M1" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msubsup><mml:mtext>I</mml:mtext><mml:mrow><mml:mtext>h</mml:mtext></mml:mrow><mml:mrow><mml:mo>+</mml:mo></mml:mrow></mml:msubsup></mml:math></inline-formula>), or do not express (<inline-formula><mml:math id="M2" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msubsup><mml:mtext>I</mml:mtext><mml:mrow><mml:mtext>h</mml:mtext></mml:mrow><mml:mrow><mml:mo>-</mml:mo></mml:mrow></mml:msubsup></mml:math></inline-formula>), 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[<sup>11</sup>]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[<sup>11</sup>]NT (0.01-0.5 μM) attenuated glutamatergic EPSC in <inline-formula><mml:math id="M3" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msubsup><mml:mtext>I</mml:mtext><mml:mrow><mml:mtext>h</mml:mtext></mml:mrow><mml:mrow><mml:mo>+</mml:mo></mml:mrow></mml:msubsup></mml:math></inline-formula> but enhanced it in <inline-formula><mml:math id="M4" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msubsup><mml:mtext>I</mml:mtext><mml:mrow><mml:mtext>h</mml:mtext></mml:mrow><mml:mrow><mml:mo>-</mml:mo></mml:mrow></mml:msubsup></mml:math></inline-formula> neurons. The attenuation effect (<inline-formula><mml:math id="M5" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msubsup><mml:mtext>I</mml:mtext><mml:mrow><mml:mtext>h</mml:mtext></mml:mrow><mml:mrow><mml:mo>+</mml:mo></mml:mrow></mml:msubsup></mml:math></inline-formula> neurons) was blocked by SR142948 (0.1 μM) while the enhancement effect (<inline-formula><mml:math id="M6" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msubsup><mml:mtext>I</mml:mtext><mml:mrow><mml:mtext>h</mml:mtext></mml:mrow><mml:mrow><mml:mo>-</mml:mo></mml:mrow></mml:msubsup></mml:math></inline-formula> 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 (<inline-formula><mml:math id="M7" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msubsup><mml:mtext>I</mml:mtext><mml:mrow><mml:mtext>h</mml:mtext></mml:mrow><mml:mrow><mml:mo>-</mml:mo></mml:mrow></mml:msubsup></mml:math></inline-formula>) neurons.</p>