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Ventral Midbrain NMDA Receptor Blockade: From Enhanced Reward and Dopamine Inactivation.

Author(s): Hernandez G, Cossette MP, Shizgal P, Rompré PP

Front Behav Neurosci. 2016;10:161 Authors: Hernandez G, Cossette MP, Shizgal P, Rompré PP

Article GUID: 27616984
17β-estradiol locally increases phasic dopamine release in the dorsal striatum.

Author(s): Shams WM, Cossette MP, Shizgal P, Brake WG

Neurosci Lett. 2018 02 05;665:29-32 Authors: Shams WM, Cossette MP, Shizgal P, Brake WG

Article GUID: 29175028
Early Adolescence is a Critical Period for the Maturation of Inhibitory Behavior.

Author(s): Reynolds LM, Yetnikoff L, Pokinko M, Wodzinski M, Epelbaum JG, Lambert LC, Cossette MP, Arvanitogiannis A, Flores C

Cereb Cortex. 2018 Oct 06;: Authors: Reynolds LM, Yetnikoff L, Pokinko M, Wodzinski M, Epelbaum JG, Lambert LC, Cossette MP, Arvanitogiannis A, Flores C

Article GUID: 30295713
The neural substrates for the rewarding and dopamine-releasing effects of medial forebrain bundle stimulation have partially discrepant frequency responses.

Author(s): Cossette MP, Conover K, Shizgal P

Behav Brain Res. 2016 Jan 15;297:345-58 Authors: Cossette MP, Conover K, Shizgal P

Article GUID: 26477378
High Oestradiol Replacement Reverses Response Memory Bias in Ovariectomised Female Rats Regardless of Dopamine Levels in the Dorsal Striatum.

Author(s): Hussain D, Cossette MP, Brake WG

J Neuroendocrinol. 2016 05;28(5): Authors: Hussain D, Cossette MP, Brake WG

Article GUID: 26929121
Title:Ventral Midbrain NMDA Receptor Blockade: From Enhanced Reward and Dopamine Inactivation.
Authors:Hernandez G,  Cossette MP,  Shizgal P,  Rompré PP
Link:https://www.ncbi.nlm.nih.gov/pubmed/27616984?dopt=Abstract
DOI:10.3389/fnbeh.2016.00161
Category:Front Behav Neurosci
PMID:27616984
Dept Affiliation: PSYCHOLOGY
1 Département de Neurosciences, Université de Montréal Montréal, QC, Canada.
2 FRQ-S Research Group in Behavioral Neurobiology, Department of Psychology, Concordia University Montréal, QC, Canada.
3 Département de Neurosciences, Université de MontréalMontréal, QC, Canada; FRQ-S Research Group in Behavioral Neurobiology, Department of Psychology, Concordia UniversityMontréal, QC, Canada.

Description:

Ventral Midbrain NMDA Receptor Blockade: From Enhanced Reward and Dopamine Inactivation.

Front Behav Neurosci. 2016;10:161

Authors: Hernandez G, Cossette MP, Shizgal P, Rompré PP

Abstract

Glutamate stimulates ventral midbrain (VM) N-Methyl-D-Aspartate receptors (NMDAR) to initiate dopamine (DA) burst firing activity, a mode of discharge associated with enhanced DA release and reward. Blockade of VM NMDAR, however, enhances brain stimulation reward (BSR), the results can be explained by a reduction in the inhibitory drive on DA neurons that is also under the control of glutamate. In this study, we used fast-scan cyclic voltammetry (FSCV) in anesthetized animals to determine whether this enhancement is associated with a change in phasic DA release in the nucleus accumbens. Rats were implanted with a stimulation electrode in the dorsal-raphe (DR) and bilateral cannulae above the VM and trained to self-administer trains of electrical stimulation. The curve-shift method was used to evaluate the effect of a single dose (0.825 nmol/0.5 µl/side) of the NMDAR antagonist, (2R,4S)-4-(3-Phosphopropyl)-2-piperidinecarboxylic acid (PPPA), on reward. These animals were then anesthetized and DA release was measured during delivery of electrical stimulation before and after VM microinjection of the vehicle followed by PPPA. As expected, phasic DA release and operant responding depended similarly on the frequency of rewarding electrical stimulation. As anticipated, PPPA produced a significant reward enhancement. Unexpectedly, PPPA produced a decrease in the magnitude of DA transients at all tested frequencies. To test whether this decrease resulted from excessive activation of DA neurons, we injected apomorphine 20 min after PPPA microinjection. At a dose (100 µg s.c.) sufficient to reduce DA firing under control conditions, apomorphine restored electrical stimulation-induced DA transients. These findings show that combined electrical stimulation and VM NMDARs blockade induce DA inactivation, an effect that indirectly demonstrates that VM NMDARs blockade enhances reward by potentiating stimulation-induced excitation in the mesoaccumbens DA pathway.

PMID: 27616984 [PubMed]