ArticlePsychopharmacology2014
NMDA receptor blockade in the prelimbic cortex activates the mesolimbic system and dopamine-dependent opiate reward signaling.
Article in Psychopharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 28 citations in OpenAlex.
- Theta oscillation synchronize VTA and mPFC during ethanol-induced conditioned place preference and stress-evoked anxiety.Translational psychiatry · 2025Article
- Ketamine and Hydroxynorketamine as Novel Pharmacotherapies for the Treatment of Opioid Use Disorders.Biological psychiatry · 2025Review
- Dissociable Roles of the mPFC-to-VTA Pathway in the Control of Impulsive Action and Risk-Related Decision-Making in Roman High- and Low-Avoidance Rats.The international journal of neuropsychopharmacology · 2024Article
- Article
- Neuronal activity of the medial prefrontal cortex, nucleus accumbens, and basolateral amygdala in conditioned taste aversion and conditioned place preference induced by different doses of morphine administrations in rats.Frontiers in pharmacology · 2023Article
- Glutamatergic Systems and Memory Mechanisms Underlying Opioid Addiction.Cold Spring Harbor perspectives in medicine · 2021Review
- A Conantokin Peptide Con-T[M8Q] Inhibits Morphine Dependence with High Potency and Low Side Effects.Marine drugs · 2021Article
- Conduct Disorder Symptoms and Illicit Drug Use in Juvenile Justice Involved Youth: The Reciprocal Relationship Between Positive Illicit Drug-Use Attitudes and Illicit Drug Use.Substance use & misuse · 2018Article
- The Role of Dopamine D1 and D3 Receptors in N-Methyl-D-Aspartate (NMDA)/GlycineB Site-Regulated Complex Cognitive Behaviors following Repeated Morphine Administration.The international journal of neuropsychopharmacology · 2017Article
- Unravelling the Link Between Prenatal Stress, Dopamine and Substance Use Disorder.Neurotoxicity research · 2017Review
- Do specific NMDA receptor subunits act as gateways for addictive behaviors?Genes, brain, and behavior · 2017Review
- Brain Reward Circuits in Morphine Addiction.Molecules and cells · 2016Review
- GABA-Mediated Inactivation of Medial Prefrontal and Agranular Insular Cortex in the Rat: Contrasting Effects on Hunger- and Palatability-Driven Feeding.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2016Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
rationaleN-Methyl-D-aspartate (NMDA) receptors in the medial prefrontal cortex (mPFC) are involved in opiate reward processing and modulate sub-cortical dopamine (DA) activity. NMDA receptor blockade in the prelimbic (PLC) division of the mPFC strongly potentiates the rewarding behavioural properties of normally sub-reward threshold doses of opiates. However, the possible functional interactions between cortical NMDA and sub-cortical DAergic motivational neural pathways underlying these effects are not understood.
objectiveThis study examines how NMDA receptor modulation in the PLC influences opiate reward processing via interactions with sub-cortical DAergic transmission. We further examined whether direct intra-PLC NMDA receptor modulation may activate DA-dependent opiate reward signaling via interactions with the ventral tegmental area (VTA).
methodsUsing an unbiased place conditioning procedure (CPP) in rats, we performed bilateral intra-PLC microinfusions of the competitive NMDA receptor antagonist, (2R)-amino-5-phosphonovaleric acid (AP-5), prior to behavioural morphine place conditioning and challenged the rewarding effects of morphine with DA receptor blockade. We next examined the effects of intra-PLC NMDA receptor blockade on the spontaneous activity patterns of presumptive VTA DA or GABAergic neurons, using single-unit, extracellular in vivo neuronal recordings.
resultsWe show that intra-PLC NMDA receptor blockade strongly activates sub-cortical DA neurons within the VTA while inhibiting presumptive non-DA GABAergic neurons. Behaviourally, NMDA receptor blockade activates a DA-dependent opiate reward system, as pharmacological blockade of DA transmission blocked morphine reward only in the presence of intra-PLC NMDA receptor antagonism.
conclusionsThese findings demonstrate a cortical NMDA-mediated mechanism controlling mesolimbic DAergic modulation of opiate reward processing.
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