Amphetamine selectively blocks inhibitory glutamate transmission in dopamine neurons

Carlos A. Paladini, Christopher D. Fiorillo, Hitoshi Morikawa, John Williams

Research output: Contribution to journalArticle

98 Citations (Scopus)

Abstract

Amphetamine is a highly addictive psychostimulant that promotes the release of the catecholamines dopamine and norepinephrine. Amphetamine-induced release of dopamine in the midbrain inhibits the activity of dopamine neurons through activation of D2 dopamine autoreceptors. Here we show that amphetamine may also excite dopamine neurons through modulation of glutamate neurotransmission. Amphetamine potently inhibits metabotropic glutamate receptor (mGluR)-mediated IPSPs in dopamine neurons, but has no effect on ionotropic glutamate receptor-mediated EPSCs. Amphetamine desensitizes the mGluR-mediated hyperpolarization through release of dopamine, activation of postsynaptic α1 adrenergic receptors, and suppression of InsP3-induced calcium release from internal stores. By selectively suppressing the inhibitory component of glutamate-mediated transmission, amphetamine may promote burst firing of dopamine neurons. Through this mechanism, amphetamine may enhance phasic release of dopamine, which is important in the neural processing of reward.

Original languageEnglish (US)
Pages (from-to)275-281
Number of pages7
JournalNature Neuroscience
Volume4
Issue number3
DOIs
StatePublished - 2001

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Dopaminergic Neurons
Amphetamine
Glutamic Acid
Dopamine
Metabotropic Glutamate Receptors
Ionotropic Glutamate Receptors
Autoreceptors
Inhibitory Postsynaptic Potentials
Mesencephalon
Reward
Synaptic Transmission
Adrenergic Receptors
Catecholamines
Norepinephrine
Calcium

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Amphetamine selectively blocks inhibitory glutamate transmission in dopamine neurons. / Paladini, Carlos A.; Fiorillo, Christopher D.; Morikawa, Hitoshi; Williams, John.

In: Nature Neuroscience, Vol. 4, No. 3, 2001, p. 275-281.

Research output: Contribution to journalArticle

Paladini, Carlos A. ; Fiorillo, Christopher D. ; Morikawa, Hitoshi ; Williams, John. / Amphetamine selectively blocks inhibitory glutamate transmission in dopamine neurons. In: Nature Neuroscience. 2001 ; Vol. 4, No. 3. pp. 275-281.
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