Prefrontal cortex–nucleus accumbens interaction: In vivo modulation by dopamine and glutamate in the prefrontal cortex

doi:10.1016/j.pbb.2008.04.011

Pharmacology Biochemistry and Behavior

Volume 90, Issue 2, August 2008, Pages 226-235

https://doi.org/10.1016/j.pbb.2008.04.011 Get rights and content

Abstract

Previous experimental studies have shown that the prefrontal cortex (PFC) regulates the activity of the nucleus accumbens (NAc), and in particular the release of dopamine in this area of the brain. In the present report we review recent microinjections/microdialysis studies from our laboratory on the effects of stimulation/blockade of dopamine and glutamate receptors in the PFC that modulate dopamine, and also acetylcholine release in the NAc. Stimulation of prefrontal D2 dopamine receptors, but not group I mGlu glutamate receptors, reduces the release of dopamine and acetylcholine in the NAc and spontaneous motor activity. This inhibitory role of prefrontal D2 receptors is not changed by acute systemic injections of the NMDA antagonist phencyclidine. On the other hand, the blockade of NMDA receptors in the PFC increases the release of dopamine and acetycholine in the NAc as well as motor activity which suggests that the hypofunction of prefrontal NMDA receptors is able to produce the neurochemical and behavioural changes associated with a dysfunction of the corticolimbic circuit. We suggest here that dopamine and glutamate receptors are, in part, segregated in specific cellular circuits in the PFC. Thus, the stimulation/blockade of these receptors would have a different net impact on PFC output projections to regulate dopamine and acetylcholine release in the NAc and in guided behaviour. Finally, it is speculated that environmental enrichment might produce plastic changes that modify the functional interaction between the PFC and the NAc in both physiological and pathological conditions.

Section snippets

Prefrontal cortex–nucleus accumbens interaction

The prefrontal cortex (PFC) has an essential role in cognition, emotion and reward (Mora and Cobo, 1990, Robbins, 2000, Öngür and Price, 2000, Fuster, 2001, Tzschentke, 2001). Experimental evidence has shown that PFC integrates sensory and limbic (emotional) information and promotes goal-directed behaviours through cortico-striatal motor loops (Robbins and Everitt, 1996, Fuster, 1997, Tzschentke and Schmidt, 2000). Relevant in this context are studies showing that PFC regulates the activity of

PFC–NAc interaction: modulation by dopamine and glutamate in the PFC

In the PFC, dopamine varicosities arising from the VTA and glutamate terminals arising from different areas of the brain—hippocampus, thalamus, amygdala and other cortical areas—impinge upon pyramidal glutamatergic neurons and GABA interneurons in the PFC (Peinado and Mora, 1986, Verney et al., 1990, Pirot et al., 1994, Bacon et al., 1996, Carr and Sesack, 1996, Carr et al., 1999, Carr and Sesack, 2000). Different types of dopamine and glutamate receptors are also localized on glutamate

PFC–NAc dysfunction: role of dopamine and glutamate receptors in the PFC

A dysfunction of the PFC–NAc interaction has been suggested to be involved in the abnormal cognitive behaviours observed in schizophrenia (Pantelis et al., 1997, Moore et al., 1999, Meyer-Lindenberg et al., 2002). Moreover, an unbalanced interaction between dopamine and glutamate inputs to the PFC could underlie the neurochemical and behavioural disturbances associated with the dysfunction of the PFC–NAc circuit (Carlsson et al., 2001, Goto and O'Donnell, 2004, Yang and Chen, 2005). In this

PFC–NAc interaction and plasticity: environmental enrichment

Environmental enrichment refers to an experimental setting in which groups of animals are housed in large cages containing tunnels, platforms, toys, running wheels that potentiates social interactions, learning and memory and sensory and motor stimulation (Rosenzweig and Bennett, 1996, van Praag et al., 2000, Mohammed et al., 2002, Mora et al., 2007a). Previous studies have shown that housing animals in an enriched environment induces changes in synaptic plasticity, increases the levels of

Final considerations

Both direct and indirect anatomical pathways are at the basis of the PFC–NAc interaction. Several studies have shown that PFC regulates the activity of the mesolimbic dopamine system. In particular, earlier in vivo studies (6-OHDA lesions and electrical stimulation) have shown that PFC regulates dopamine release in the NAc. In the present review, we focused on the specific role of dopamine and glutamate receptors in the PFC that modulate the activity of dopamine, and also acetylcholine, in the

Acknowledgement

This research was supported by SAF2003-0448, SAF2006-01554 and UCM/CM2006-921069.

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ReviewPrefrontal cortex–nucleus accumbens interaction: In vivo modulation by dopamine and glutamate in the prefrontal cortex

Abstract

Section snippets

Prefrontal cortex–nucleus accumbens interaction

PFC–NAc interaction: modulation by dopamine and glutamate in the PFC

PFC–NAc dysfunction: role of dopamine and glutamate receptors in the PFC

PFC–NAc interaction and plasticity: environmental enrichment

Final considerations

Acknowledgement

Brain Res

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Pharmacol Biochem Behav

Brain Res

Brain and Cognition

Behav Brain Res

Brain Res

Neuron

Brain Res Rev

Physiol Behav

Biol Psychiatry

Trends Neurosci

Dev Brain Res

Biol Psychiatry

J Chem Neuroanat

Neuropsychopharmacology

Neuron

Neuroscience

Neuroscience

Neuroscience

Pharmacol Biochem Behav

Eur J Pharmacol

Prog Neurobiol

Biol Psychiatry

Progress in Brain Research Elsevier

Neuroscience

Biol Psychiatry

Brain Res Rev

Brain Res

Neurosci Lett

Brain Res

Neuroscience

Neuroscience

Prog Brain Res

Curr Opin Neurobiol

Behav Brain Res

Pharmacol Biochem Behav

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Psychopharmacology

Prefrontal DA transmission at D1 receptors and the pathology of schizophrenia

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J Neurosci

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Intra-medial prefrontal cortex injection of quinpirole, but not SKF 38393, blocks the acute motor-stimulant response to cocaine in the rat

Psychopharmacology

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J Neurosci

Association of ketamine-induced psychosis with focal activation of the prefrontal cortex in healthy volunteers

Am J Psychiatry

Interactions between monoamines, glutamate, and GABA in schizophrenia: new evidence

Annu Rev Pharmacol Toxicol

Dopamine terminals in the rat prefrontal cortex synapse on pyramidal cells that project to the nucleus accumbens

J Neurosci

Hippocampal afferents to the rat prefrontal cortex: synaptic targets and relation to dopamine terminals

J Comp Neurol

Projections from the rat prefrontal cortex to the ventral tegmental area: target specificity in the synaptic associations with mesoaccumbens and mesocortical neurons

J Neurosci

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Synapse

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Eur J Neurosci

Review
Prefrontal cortex–nucleus accumbens interaction: In vivo modulation by dopamine and glutamate in the prefrontal cortex