Modulation of dopamine neuronal activity by glutamate receptor subtypes

Meltzer, Leonard T.; Christoffersen, Curt; Serpa, Kevin A.

doi:10.1016/s0149-7634(96)00030-9

Cited by 85 publications

(58 citation statements)

References 85 publications

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“…Neurons of the substantia nigra are predominantly involved in the nigralstriatal motor circuits, whereas neurons from the VTA are involved in corticolimbic circuits, which include the nucleus accumbens and the PFC. Dopaminergic neurons in the substantia nigra and the VTA receive glutamatergic inputs (Carr et al, 1999;Carr & Sesack, 2000;Counihan et al, 1998;Gauchy et al, 1994;Smith et al, 1996), and gluta-mate stimulates dopaminergic activity (Meltzer et al, 1997). Conversely, the glutamate system is inhibited by dopamine and facilitated by the inhibition of D 2 receptors.…”

Section: Antipsychotic Drugs Modulate N-methyl-d-aspartate Receptor Amentioning

confidence: 99%

Molecular aspects of glutamate dysregulation: implications for schizophrenia and its treatment

Konradi

Heckers

2003

Pharmacology & Therapeutics

294

165

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The glutamate system is involved in many aspects of neuronal synaptic strength and function during development and throughout life. Synapse formation in early brain development, synapse maintenance, and synaptic plasticity are all influenced by the glutamate system. The number of neurons and the number of their connections are determined by the activity of the glutamate system and its receptors. Malfunctions of the glutamate system affect neuroplasticity and can cause neuronal toxicity. In schizophrenia, many glutamate-regulated processes seem to be perturbed. Abnormal neuronal development, abnormal synaptic plasticity, and neurodegeneration have been proposed to be causal or contributing factors in schizophrenia. Interestingly, it seems that the glutamate system is dysregulated and that N-methyl-D-aspartate receptors operate at reduced activity. Here we discuss how the molecular aspects of glutamate malfunction can explain some of the neuropathology observed in schizophrenia, and how the available treatment intervenes through the glutamate system.

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Section: Antipsychotic Drugs Modulate N-methyl-d-aspartate Receptor Amentioning

confidence: 99%

Molecular aspects of glutamate dysregulation: implications for schizophrenia and its treatment

Konradi

Heckers

2003

Pharmacology & Therapeutics

294

165

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“…Previous reports on the electrophysiological and neurochemical effects of reducing serotonin tone in the ventral tegmental area and accumbens, respectively, indicate mixed effects depending in part on the serotonin receptor subtype examined and the basal activity of the dopamine cells (Imperato and Angelucci, 1989;Chen and Reith, 1994;Di Mascio and Esposito, 1997;Lejeune and Millan, 1998;Parsons et al, 1999). A contributing factor to the enhanced dopamine release may be the rise in extracellular glutamate produced by the combination of intra-DRN DPAT and acute cocaine since, in some studies, glutamate receptor stimulation enhances dopamine release (Meltzer et al, 1997;Whitton, 1997 for reviews). While the source of elevated glutamate was not identified in the present study, serotonergic projections from the DRN innervate densely the cortical and allocortical regions supplying glutamate to the accumbens, including the prefrontal cortex, hippocampus, thalamus, and amygdala (eg Vertes, 1991).…”

Section: Serotonin Projections From the Drn Regulate The Acute Effectmentioning

confidence: 99%

Dissociable Roles for the Dorsal and Median Raphé in the Facilitatory Effect of 5-HT1A Receptor Stimulation upon Cocaine-Induced Locomotion and Sensitization

Szumlinski

Frys

Kalivas

2004

Neuropsychopharmacol

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A distinct role for serotonin transmission from the dorsal and median raphé nuclei (DRN and MRN, respectively) was identified in regulating the behavioral and neurochemical effects of acute and repeated cocaine administration. Serotonin 1A (5-hydroxytryptophan (5-HT)1A) receptors were stimulated by intraraphé microinjection of 8-hydroxy-2-(di-n-propylamino)tetralin (DPAT; 5 or 10 mg) and behavior, as well as extracellular neurotransmitter content in the nucleus accumbens was measured. Pretreatment of the DRN with DPAT caused a sensitization-like potentiation of acute cocaine-induced motor activity and an elevation in extracellular dopamine and glutamate. In contrast, DPAT microinjection into the MRN did not alter acute cocaine-induced motor activity or extracellular levels of dopamine or glutamate. Acutely, DPAT microinjection into either raphé nucleus reduced the basal and acute cocaine-stimulated levels of extracellular serotonin. Pretreatment with DPAT before systemic cocaine administration was continued for 5 days, and 3 weeks after the last injection, all rats were administered a cocaine challenge injection. The sensitized behavioral and neurochemical response produced by repeated cocaine in control subjects was unaffected by the intra-DRN administration of DPAT. However, in animals administered DPAT into the MRN, both the sensitized motor response and the increase in glutamate were augmented, while the sensitized serotonin response was blocked, without altering dopamine sensitization. These data show a differential role for 5-HT1A receptors in the DRN and MRN in the acute and sensitized effects of cocaine. While the DRN is involved in the acute effects of cocaine, neuroadaptations in the MRN may regulate the long-term consequences of repeated cocaine exposure.

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“…Considering that glutamate afferents control burst firing of dopamine neurons in vivo (Meltzer et al, 1997), it is tempting to propose that glutamatergic neurons innervating the VTA are involved in the clonidine-mediated activation of DA neurons during withdrawal. We recently demonstrated that the ventrolateral subregion of the BNST sends a strong glutamate projection to the VTA (Georges and Aston-Jones, 2002).…”

Section: Clonidine Modulates the Noradrenaline-dopamine Interaction Dmentioning

confidence: 99%

Prolonged Activation of Mesolimbic Dopaminergic Neurons by Morphine Withdrawal Following Clonidine: Participation of Imidazoline and Norepinephrine Receptors

Georges

Aston‐Jones

2003

Neuropsychopharmacol

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The a2 adrenoceptor (a2R) agonist clonidine is used as a treatment for heroin addiction. Substantial evidence indicates that dopaminergic and noradrenergic systems have key roles in opiate dependence and withdrawal but the possible interactions between these two pathways remain unclear. The objective of this study was to establish the effects of clonidine pretreatment on ventral tegmental area dopaminergic (VTA DA) neuronal activity during morphine withdrawal. Responses of VTA DA neurons to withdrawal precipitated by naltrexone were characterized in anesthetized rats using extracellular recordings. As expected, withdrawal produced a marked inhibition of VTA DA neuronal activity. However, pretreatment with clonidine prevented this inhibition induced by withdrawal, and instead produced a long-lasting activation of firing rate (+50%) and burst firing (+19%). In contrast, pretreatment with a more selective a2R agonist, UK14304, did not prevent the inhibition of VTA DA neuron activity during withdrawal. We tested whether the high affinity of clonidine for imidazoline-1 receptors (I1Rs) was responsible for the difference between these two a2R agonists. In morphine-dependent rats pretreated with rilmenidine (mixed a2R/I1R agonist), precipitation of withdrawal elicited a 22% increase of VTA DA impulse activity. The action of clonidine on I1Rs was studied by coadministering clonidine with RX821002, a specific a2R antagonist. Pretreatment with RX821002 plus clonidine prevented the inhibition of VTA DA activity during withdrawal but failed to produce excitation. These results indicate that the pharmacological effects of clonidine on VTA DA neurons during morphine withdrawal is related to actions on I1Rs as well as a2Rs.

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Modulation of dopamine neuronal activity by glutamate receptor subtypes

Cited by 85 publications

References 85 publications

Molecular aspects of glutamate dysregulation: implications for schizophrenia and its treatment

Molecular aspects of glutamate dysregulation: implications for schizophrenia and its treatment

Dissociable Roles for the Dorsal and Median Raphé in the Facilitatory Effect of 5-HT1A Receptor Stimulation upon Cocaine-Induced Locomotion and Sensitization

Prolonged Activation of Mesolimbic Dopaminergic Neurons by Morphine Withdrawal Following Clonidine: Participation of Imidazoline and Norepinephrine Receptors

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