Excitotoxic lesions of the pedunculopontine differentially mediate morphine- and d-amphetamine-evoked striatal dopamine efflux and behaviors

A. D. Miller, Gina L Forster, K. M. Metcalf, C. D. Blaha

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Cholinergic and glutamatergic cells in the pedunculopontine tegmental nucleus are a principal source of excitatory input to midbrain dopamine neurons projecting to the striatum. Disruption of these brainstem inputs has been shown to respectively enhance and reduce psychostimulant and opiate self-administration in rats. In the present study, d-amphetamine- and morphine-induced behaviors and dorsal striatal dopamine efflux, measured using in vivo chronoamperometry, were investigated 21 days after bilateral excitotoxic (ibotenate) lesions of the pedunculopontine in rats. Compared to sham-operated controls, pedunculopontine lesions enhanced stereotyped behaviors induced by a challenge injection of d-amphetamine (1.5 mg/kg, i.p.) to an extent that markedly interfered with the expression of locomotor behavior. A significant augmentation in striatal dopamine efflux was also observed in these lesioned animals under urethane anesthesia in response to a similar challenge injection of d-amphetamine (1.5 mg/kg, i.v.) 2 days following these behavioral observations. In direct contrast, pedunculopontine lesions in a separate group of rats significantly attenuated morphine-induced (2 mg/kg, i.p.) stereotyped activity, although no significant differences were observed in locomotion compared to sham-operated animals. Under urethane anesthesia, these lesions attenuated striatal dopamine efflux evoked by a similar challenge injection of morphine (2 mg/kg, i.v.). These findings indicate that the pedunculopontine differentially mediates the pharmacological actions of two diverse drugs of abuse on striatal dopamine neurotransmission and resultant behaviors. These results also imply that the pedunculopontine tegmental nucleus may serve as a major striatal-motor interface in the processing of salient environmental stimuli, and their incentive rewarding impact on dopamine-mediated behavioral responses.

Original languageEnglish (US)
Pages (from-to)351-362
Number of pages12
JournalNeuroscience
Volume111
Issue number2
DOIs
StatePublished - May 10 2002

Fingerprint

Corpus Striatum
Dextroamphetamine
Morphine
Dopamine
Pedunculopontine Tegmental Nucleus
Urethane
Injections
Opiate Alkaloids
Anesthesia
Stereotyped Behavior
Self Administration
Dopaminergic Neurons
Street Drugs
Locomotion
Mesencephalon
Synaptic Transmission
Cholinergic Agents
Brain Stem
Motivation
Pharmacology

Keywords

  • Dorsal striatum
  • Ibotenate
  • Locomotion
  • Mesopontine
  • Stereotypy
  • Voltammetry

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Excitotoxic lesions of the pedunculopontine differentially mediate morphine- and d-amphetamine-evoked striatal dopamine efflux and behaviors. / Miller, A. D.; Forster, Gina L; Metcalf, K. M.; Blaha, C. D.

In: Neuroscience, Vol. 111, No. 2, 10.05.2002, p. 351-362.

Research output: Contribution to journalArticle

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