Impact of metabotropic glutamate 2/3 receptor stimulation on activated dopamine release and locomotion

Alan Pehrson, Bita Moghaddam

Research output: Contribution to journalArticleResearchpeer-review

25 Citations (Scopus)

Abstract

Rationale: Activation of metabotropic glutamate (mGlu) 2/3 receptors may provide a novel strategy for treating schizophrenia. This effect is thought to be mediated through dopamine-independent mechanisms because mGlu2/3-receptor agonists have no considerable affinity for dopamine receptors. These agonists, however, reduce amphetamine-induced hyperlocomotion suggesting that they influence dopamine neurotransmission. Objective: We evaluated whether the inhibitory effect of mGlu2/3-receptor activation on amphetamine-induced hyperlocomotion correlates with attenuated dopamine release. We also assessed whether mGlu 2/3 receptor activation has inhibitory effects on activity-dependent vesicular release of dopamine in behaving animals. Methods: Microdialysis was used to measure extracellular levels of dopamine in the dorsal striatum (DStr) and nucleus accumbens (NAc) of freely moving rats. The effect of the mGlu2/3-receptor agonist LY354740 on dopamine release and locomotion elicited by amphetamine, electrical stimulation of the ventral tegmental area, or L-dopa was assessed. Results: We find that the inhibitory effect of mGlu2/3 activation on amphetamine-induced hyperlocomotion correlates with an attenuated increase in dopamine release in the NAc and DStr. However, when dopamine levels were increased by electrical stimulation of dopamine neurons or by administration of the dopamine precursor L-dopa, activation of mGlu2/3 receptors had no effect on dopamine release or on behavior. Conclusions: Activation of mGlu2/3 receptors attenuates amphetamine-induced dopamine release through a mechanism that does not affect activity dependent vesicular release, reuptake or synthesis of dopamine.

Original languageEnglish
Pages (from-to)443-455
Number of pages13
JournalPsychopharmacology
Volume211
Issue number4
DOIs
StatePublished - 1 Sep 2010

Fingerprint

Locomotion
Dopamine
Amphetamine
Nucleus Accumbens
Levodopa
Electric Stimulation
metabotropic glutamate receptor 3
metabotropic glutamate receptor 2
eglumetad
Ventral Tegmental Area
Dopaminergic Neurons
Microdialysis
Dopamine Receptors
Synaptic Transmission
Schizophrenia

Keywords

  • Amphetamine
  • Antipsychotic
  • Microdialysis
  • Nucleus accumbens
  • Schizophrenia
  • Striatum

Cite this

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abstract = "Rationale: Activation of metabotropic glutamate (mGlu) 2/3 receptors may provide a novel strategy for treating schizophrenia. This effect is thought to be mediated through dopamine-independent mechanisms because mGlu2/3-receptor agonists have no considerable affinity for dopamine receptors. These agonists, however, reduce amphetamine-induced hyperlocomotion suggesting that they influence dopamine neurotransmission. Objective: We evaluated whether the inhibitory effect of mGlu2/3-receptor activation on amphetamine-induced hyperlocomotion correlates with attenuated dopamine release. We also assessed whether mGlu 2/3 receptor activation has inhibitory effects on activity-dependent vesicular release of dopamine in behaving animals. Methods: Microdialysis was used to measure extracellular levels of dopamine in the dorsal striatum (DStr) and nucleus accumbens (NAc) of freely moving rats. The effect of the mGlu2/3-receptor agonist LY354740 on dopamine release and locomotion elicited by amphetamine, electrical stimulation of the ventral tegmental area, or L-dopa was assessed. Results: We find that the inhibitory effect of mGlu2/3 activation on amphetamine-induced hyperlocomotion correlates with an attenuated increase in dopamine release in the NAc and DStr. However, when dopamine levels were increased by electrical stimulation of dopamine neurons or by administration of the dopamine precursor L-dopa, activation of mGlu2/3 receptors had no effect on dopamine release or on behavior. Conclusions: Activation of mGlu2/3 receptors attenuates amphetamine-induced dopamine release through a mechanism that does not affect activity dependent vesicular release, reuptake or synthesis of dopamine.",
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Impact of metabotropic glutamate 2/3 receptor stimulation on activated dopamine release and locomotion. / Pehrson, Alan; Moghaddam, Bita.

In: Psychopharmacology, Vol. 211, No. 4, 01.09.2010, p. 443-455.

Research output: Contribution to journalArticleResearchpeer-review

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