Modulation of dopamine efflux in the striatum following cholinergic stimulation of the substantia nigra in intact and pedunculopontine tegmental nucleus-lesioned rats

C. D. Blaha, P. Winn

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131 Citations (Scopus)

Abstract

The effects of microinjections of cholinergic agents into the substantia nigra pars compacta on dopamine (DA) efflux in the anterior dorsomedial striatum of urethane-anesthetized rats were investigated using in vivo chronoamperometry and intracerebral microdialysis techniques. A dose- dependent augmentation of DA efflux as evidenced by increases in the chronoamperometric signals was observed in the striatum following nigral microinjections of the cholinergic agonists nicotine or carbachol. Enhancing extracellular concentrations of ACh in the substantia nigra by intranigral infusions of the cholinesterase inhibitor neostigmine also resulted in an increase in the chronoamperometric signal corresponding to DA overflow in the striatum. These stimulatory effects of neostigmine on DA efflux in the striatum were confirmed using in vivo microdialysis. Compared to sham- operated control animals, quinolinic acid lesions of the pedunculopontine tegmental nucleus (PPTg) resulted in an attenuation of the stimulatory effects of intranigral neostigmine on DA efflux in the striatum. In contrast, these treatments resulted in an enhancement of striatal DA efflux in response to nigral infusions of the direct ACh receptor agonist nicotine. Combined, these data suggest that PPTg cholinergic neurons are indirectly involved in regulating the activity of the striatum by modulating the activity of DA neurons in the substantia nigra of the rat.

LanguageEnglish
Pages1035-1044
Number of pages10
JournalJournal of Neuroscience
Volume13
Issue number3
Publication statusPublished - 1 Jan 1993

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Pedunculopontine Tegmental Nucleus
Substantia Nigra
Cholinergic Agents
Dopamine
Neostigmine
Microdialysis
Microinjections
Nicotine
Quinolinic Acid
Corpus Striatum
Cholinergic Agonists
Cholinergic Neurons
Dopaminergic Neurons
Urethane
Cholinesterase Inhibitors
Carbachol
Cholinergic Receptors

Keywords

  • ACh
  • chronoamperometry
  • dialysis
  • dopamine
  • pedunculopontine tegmental nucleus
  • quinolinate
  • rat
  • striatum
  • substantia nigra
  • acetylcholine
  • cholinergic receptor
  • neostigmine
  • quinolinic acid
  • amperometry
  • animal tissue
  • dose response
  • drug effect
  • nerve conduction

Cite this

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title = "Modulation of dopamine efflux in the striatum following cholinergic stimulation of the substantia nigra in intact and pedunculopontine tegmental nucleus-lesioned rats",
abstract = "The effects of microinjections of cholinergic agents into the substantia nigra pars compacta on dopamine (DA) efflux in the anterior dorsomedial striatum of urethane-anesthetized rats were investigated using in vivo chronoamperometry and intracerebral microdialysis techniques. A dose- dependent augmentation of DA efflux as evidenced by increases in the chronoamperometric signals was observed in the striatum following nigral microinjections of the cholinergic agonists nicotine or carbachol. Enhancing extracellular concentrations of ACh in the substantia nigra by intranigral infusions of the cholinesterase inhibitor neostigmine also resulted in an increase in the chronoamperometric signal corresponding to DA overflow in the striatum. These stimulatory effects of neostigmine on DA efflux in the striatum were confirmed using in vivo microdialysis. Compared to sham- operated control animals, quinolinic acid lesions of the pedunculopontine tegmental nucleus (PPTg) resulted in an attenuation of the stimulatory effects of intranigral neostigmine on DA efflux in the striatum. In contrast, these treatments resulted in an enhancement of striatal DA efflux in response to nigral infusions of the direct ACh receptor agonist nicotine. Combined, these data suggest that PPTg cholinergic neurons are indirectly involved in regulating the activity of the striatum by modulating the activity of DA neurons in the substantia nigra of the rat.",
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AU - Winn, P.

PY - 1993/1/1

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N2 - The effects of microinjections of cholinergic agents into the substantia nigra pars compacta on dopamine (DA) efflux in the anterior dorsomedial striatum of urethane-anesthetized rats were investigated using in vivo chronoamperometry and intracerebral microdialysis techniques. A dose- dependent augmentation of DA efflux as evidenced by increases in the chronoamperometric signals was observed in the striatum following nigral microinjections of the cholinergic agonists nicotine or carbachol. Enhancing extracellular concentrations of ACh in the substantia nigra by intranigral infusions of the cholinesterase inhibitor neostigmine also resulted in an increase in the chronoamperometric signal corresponding to DA overflow in the striatum. These stimulatory effects of neostigmine on DA efflux in the striatum were confirmed using in vivo microdialysis. Compared to sham- operated control animals, quinolinic acid lesions of the pedunculopontine tegmental nucleus (PPTg) resulted in an attenuation of the stimulatory effects of intranigral neostigmine on DA efflux in the striatum. In contrast, these treatments resulted in an enhancement of striatal DA efflux in response to nigral infusions of the direct ACh receptor agonist nicotine. Combined, these data suggest that PPTg cholinergic neurons are indirectly involved in regulating the activity of the striatum by modulating the activity of DA neurons in the substantia nigra of the rat.

AB - The effects of microinjections of cholinergic agents into the substantia nigra pars compacta on dopamine (DA) efflux in the anterior dorsomedial striatum of urethane-anesthetized rats were investigated using in vivo chronoamperometry and intracerebral microdialysis techniques. A dose- dependent augmentation of DA efflux as evidenced by increases in the chronoamperometric signals was observed in the striatum following nigral microinjections of the cholinergic agonists nicotine or carbachol. Enhancing extracellular concentrations of ACh in the substantia nigra by intranigral infusions of the cholinesterase inhibitor neostigmine also resulted in an increase in the chronoamperometric signal corresponding to DA overflow in the striatum. These stimulatory effects of neostigmine on DA efflux in the striatum were confirmed using in vivo microdialysis. Compared to sham- operated control animals, quinolinic acid lesions of the pedunculopontine tegmental nucleus (PPTg) resulted in an attenuation of the stimulatory effects of intranigral neostigmine on DA efflux in the striatum. In contrast, these treatments resulted in an enhancement of striatal DA efflux in response to nigral infusions of the direct ACh receptor agonist nicotine. Combined, these data suggest that PPTg cholinergic neurons are indirectly involved in regulating the activity of the striatum by modulating the activity of DA neurons in the substantia nigra of the rat.

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KW - striatum

KW - substantia nigra

KW - acetylcholine

KW - cholinergic receptor

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KW - quinolinic acid

KW - amperometry

KW - animal tissue

KW - dose response

KW - drug effect

KW - nerve conduction

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