Effect of D1- and D2-like Dopamine Receptor Antagonists on the Rewarding and Anxiolytic Effects of Neurotensin in the Ventral Pallidum

Abstract

Background: Neurotensin (NT) acts as a neurotransmitter and neuromodulator in the central nervous system. It was shown previously that NT in the ventral pallidum (VP) has rewarding and anxiolytic effects. NT exerts its effect in interaction with dopamine (DA) receptors in numerous brain areas; however, this has not yet been investigated in the VP. The aim of this study was to examine whether the inhibition of D1-like and D2-like DA receptors of the VP can modify the above mentioned effects of NT. Methods: Microinjection cannulas were implanted by means of stereotaxic operations into the VP of male Wistar rats. The rewarding effect of NT was examined by means of a conditioned place preference test. Anxiety was investigated with an elevated plus maze test. To investigate the possible interaction, D1-like DA receptor antagonist SCH23390 or D2-like DA receptor antagonist sulpiride were microinjected prior to NT. All of the drugs were also injected independently to analyze their effects alone. Results: In the present experiments, both the rewarding and anxiolytic effects of NT in the VP were prevented by both D1-like and D2-like DA receptor antagonists. Administered on their own, the antagonists did not influence reward and anxiety. Conclusion: Our present results show that the activity of the D1-like and D2-like DA receptors of the VP is a necessary requirement for both the rewarding and anxiolytic effects of NT.

The Neurobiological Underpinnings of Obsessive-Compulsive Symptoms in Psychosis, Translational Issues for Treatment-Resistant Schizophrenia

“…It is involved in cognitive and affective processes, including reward processing [ 131 ], which may shape the “cognitive and reward side” of OCS. Regarding reward and anxiolytic effects, a recent preclinical study focused on the role of neurotensin and its regulation by D1-like and D2-like receptors antagonists (i.e., SCH23390 and sulpiride) that are able to revert these effects [ 132 ]. Despite no evidence confirming its direct link with OCD or OCS, neurotensin could have a role in neurotoxicity by activating NMDAR, resulting in further activation of glutamatergic loops that are hyperactive in OCD [ 133 , 134 ].…”