Pedunculopontine tegmental stimulation evokes striatal dopamine efflux by activation of acetylcholine and glutamate receptors in the midbrain and pons of the rat

Gina L. Forster, Charles D. Blaha

Research output: Contribution to journalArticle

122 Citations (Scopus)

Abstract

The pedunculopontine tegmental nucleus appears to influence striatal dopamine activity via cholinergic and glutamatergic afferents to dopaminergic cells of the substantia nigra pars compacta. We measured changes in striatal dopamine oxidation current (dopamine efflux) in response to electrical stimulation of the pedunculopontine tegmental nucleus using in vivo electrochemistry in urethane-anaesthetized rats. Pedunculopontine tegmental nucleus stimulation evoked a three-component change in striatal dopamine efflux, consisting of: (i) an initial rapid increase of 2 min duration; followed by (ii) a decrease below prestimulation levels of 9 min duration; then by (iii) a prolonged increase lasting 35 min. Intra-nigral infusions of the ionotropic glutamate receptor antagonist kynurenate (10 μg/μL) or the nicotinic cholinergic receptor antagonist mecamylamine (5 μg/0.5 μL) selectively attenuated the rapid first component, while systemic injections of the muscarinic cholinergic antagonist scopolamine (5 mg/kg, i.p.) diminished the second and third components. In addition, intra-pedunculopontine tegmental nucleus infusions of the M2 muscarinic antagonist methoctramine (50 μg/μL) selectively abolished the inhibitory second component, while intranigral infusions of scopolamine (200 μg/μL) selectively abolished the prolonged third component. Intra-nigral infusions of the metabotropic glutamate receptor antagonist (+)-α-methyl-4-carboxyphenylglycine (2 μg/μL) had no effect on pedunculopontine tegmental nucleus-elicited striatal dopamine efflux. These results suggest that the pedunculopontine tegmental nucleus utilizes nicotinic and ionotropic glutamate receptors in the substantia nigra to mediate rapid activation, M2-like muscarinic autoreceptors in the pedunculopontine tegmental nucleus to mediate decreased activation, and muscarinic receptors in the substantia nigra (probably of the M5 subtype) to mediate prolonged activation, of the nigrostriatal dopaminergic system.

Original languageEnglish (US)
Pages (from-to)751-762
Number of pages12
JournalEuropean Journal of Neuroscience
Volume17
Issue number4
DOIs
StatePublished - Feb 1 2003

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Pedunculopontine Tegmental Nucleus
Corpus Striatum
Pons
Glutamate Receptors
Cholinergic Receptors
Mesencephalon
Dopamine
Substantia Nigra
Ionotropic Glutamate Receptors
Excitatory Amino Acid Antagonists
Muscarinic Antagonists
Scopolamine Hydrobromide
Cholinergic Agents
alpha-methyl-4-carboxyphenylglycine
Kynurenic Acid
Mecamylamine
Electrochemistry
Autoreceptors
Metabotropic Glutamate Receptors
Urethane

Keywords

  • Muscarinic receptors
  • Nicotinic receptors
  • Substantia nigra
  • Voltammetry

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

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title = "Pedunculopontine tegmental stimulation evokes striatal dopamine efflux by activation of acetylcholine and glutamate receptors in the midbrain and pons of the rat",
abstract = "The pedunculopontine tegmental nucleus appears to influence striatal dopamine activity via cholinergic and glutamatergic afferents to dopaminergic cells of the substantia nigra pars compacta. We measured changes in striatal dopamine oxidation current (dopamine efflux) in response to electrical stimulation of the pedunculopontine tegmental nucleus using in vivo electrochemistry in urethane-anaesthetized rats. Pedunculopontine tegmental nucleus stimulation evoked a three-component change in striatal dopamine efflux, consisting of: (i) an initial rapid increase of 2 min duration; followed by (ii) a decrease below prestimulation levels of 9 min duration; then by (iii) a prolonged increase lasting 35 min. Intra-nigral infusions of the ionotropic glutamate receptor antagonist kynurenate (10 μg/μL) or the nicotinic cholinergic receptor antagonist mecamylamine (5 μg/0.5 μL) selectively attenuated the rapid first component, while systemic injections of the muscarinic cholinergic antagonist scopolamine (5 mg/kg, i.p.) diminished the second and third components. In addition, intra-pedunculopontine tegmental nucleus infusions of the M2 muscarinic antagonist methoctramine (50 μg/μL) selectively abolished the inhibitory second component, while intranigral infusions of scopolamine (200 μg/μL) selectively abolished the prolonged third component. Intra-nigral infusions of the metabotropic glutamate receptor antagonist (+)-α-methyl-4-carboxyphenylglycine (2 μg/μL) had no effect on pedunculopontine tegmental nucleus-elicited striatal dopamine efflux. These results suggest that the pedunculopontine tegmental nucleus utilizes nicotinic and ionotropic glutamate receptors in the substantia nigra to mediate rapid activation, M2-like muscarinic autoreceptors in the pedunculopontine tegmental nucleus to mediate decreased activation, and muscarinic receptors in the substantia nigra (probably of the M5 subtype) to mediate prolonged activation, of the nigrostriatal dopaminergic system.",
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N2 - The pedunculopontine tegmental nucleus appears to influence striatal dopamine activity via cholinergic and glutamatergic afferents to dopaminergic cells of the substantia nigra pars compacta. We measured changes in striatal dopamine oxidation current (dopamine efflux) in response to electrical stimulation of the pedunculopontine tegmental nucleus using in vivo electrochemistry in urethane-anaesthetized rats. Pedunculopontine tegmental nucleus stimulation evoked a three-component change in striatal dopamine efflux, consisting of: (i) an initial rapid increase of 2 min duration; followed by (ii) a decrease below prestimulation levels of 9 min duration; then by (iii) a prolonged increase lasting 35 min. Intra-nigral infusions of the ionotropic glutamate receptor antagonist kynurenate (10 μg/μL) or the nicotinic cholinergic receptor antagonist mecamylamine (5 μg/0.5 μL) selectively attenuated the rapid first component, while systemic injections of the muscarinic cholinergic antagonist scopolamine (5 mg/kg, i.p.) diminished the second and third components. In addition, intra-pedunculopontine tegmental nucleus infusions of the M2 muscarinic antagonist methoctramine (50 μg/μL) selectively abolished the inhibitory second component, while intranigral infusions of scopolamine (200 μg/μL) selectively abolished the prolonged third component. Intra-nigral infusions of the metabotropic glutamate receptor antagonist (+)-α-methyl-4-carboxyphenylglycine (2 μg/μL) had no effect on pedunculopontine tegmental nucleus-elicited striatal dopamine efflux. These results suggest that the pedunculopontine tegmental nucleus utilizes nicotinic and ionotropic glutamate receptors in the substantia nigra to mediate rapid activation, M2-like muscarinic autoreceptors in the pedunculopontine tegmental nucleus to mediate decreased activation, and muscarinic receptors in the substantia nigra (probably of the M5 subtype) to mediate prolonged activation, of the nigrostriatal dopaminergic system.

AB - The pedunculopontine tegmental nucleus appears to influence striatal dopamine activity via cholinergic and glutamatergic afferents to dopaminergic cells of the substantia nigra pars compacta. We measured changes in striatal dopamine oxidation current (dopamine efflux) in response to electrical stimulation of the pedunculopontine tegmental nucleus using in vivo electrochemistry in urethane-anaesthetized rats. Pedunculopontine tegmental nucleus stimulation evoked a three-component change in striatal dopamine efflux, consisting of: (i) an initial rapid increase of 2 min duration; followed by (ii) a decrease below prestimulation levels of 9 min duration; then by (iii) a prolonged increase lasting 35 min. Intra-nigral infusions of the ionotropic glutamate receptor antagonist kynurenate (10 μg/μL) or the nicotinic cholinergic receptor antagonist mecamylamine (5 μg/0.5 μL) selectively attenuated the rapid first component, while systemic injections of the muscarinic cholinergic antagonist scopolamine (5 mg/kg, i.p.) diminished the second and third components. In addition, intra-pedunculopontine tegmental nucleus infusions of the M2 muscarinic antagonist methoctramine (50 μg/μL) selectively abolished the inhibitory second component, while intranigral infusions of scopolamine (200 μg/μL) selectively abolished the prolonged third component. Intra-nigral infusions of the metabotropic glutamate receptor antagonist (+)-α-methyl-4-carboxyphenylglycine (2 μg/μL) had no effect on pedunculopontine tegmental nucleus-elicited striatal dopamine efflux. These results suggest that the pedunculopontine tegmental nucleus utilizes nicotinic and ionotropic glutamate receptors in the substantia nigra to mediate rapid activation, M2-like muscarinic autoreceptors in the pedunculopontine tegmental nucleus to mediate decreased activation, and muscarinic receptors in the substantia nigra (probably of the M5 subtype) to mediate prolonged activation, of the nigrostriatal dopaminergic system.

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