Elsevier

Behavioural Brain Research

Volume 39, Issue 3, 20 August 1990, Pages 230-239
Behavioural Brain Research

Research report
Excitatory amino acid pathways in brain-stimulation reward

https://doi.org/10.1016/0166-4328(90)90029-EGet rights and content

Abstract

A range of agonists and antagonists active at different glutamate/aspartate (Glu/Asp) receptor subtypes were injected into rat ventral tegmental (VTA) sites downstream from self-stimulation electrodes in the medial forebrain bundle. Control injections were made into the contralateral tegmentum. Variable-interval (VI 10 s) self-stimulation was not significantly affected by a specific antagonist of N-methyl-d-aspartate (NMDA)-type receptors (d,l-2-amino-5-phosphonovaleric acid (2-AP5), 10 and 50 nmol). Broad-spectrum excitatory amino acid (EAA) antagonists viz cis-2,3-piperidine dicarboxylate (cPDA) (10 and 50 nmol), γ-d-glutamylaminomethyl sulphonic acid (GAMS) (10 nmol) and p-chlorobenzoyl-2,3-piperazine dicarboxylic acid (pCB PzDA) (2.0 and 10 nmol), active at kainate, quisqualate, as well as NMDA receptors, all produced significant depression of responding when injected into the ipsilateral, but not the contralateral, tegmentum. Compounds inhibiting Glu/Asp reuptake had variable effects: strong depression with dihydrokainic acid (7.5 nmol), or no significant effect (l-threo-3-hydroxyaspartic acid, 2.0 and 10 nmol). The receptor agonist, NMDA (10 nmol), depressed responding regardless of injection side; kainic and quisqualic acid elicited myoclonic and other non-specific responses in preliminary tests, and were not examined further; enhanced responding was not seen. The side-specific blockade of responding by non-NMDA antagonists indicates the existence of non-NMDA EAA terminals in the VTA, signalling the receipt of hypothalamic brain-stimulation reward. Caudally directed EAA projections terminating on A10 dopamine cell bodies may account for depression of self-stimulation by EAA antagonists.

References (42)

  • A.G. Phillips et al.

    Dopaminergic substrates of intracranial self-stimulation

    Brain Res.

    (1976)
  • C.J. Pycock et al.

    Acute motor effects of N-methyl-d-aspartic acid and kainic acid applied focally to mesencephalic dopaminergic cell body regions in the rat

    Neurosci. Lett.

    (1980)
  • I.C. Rose et al.

    Chronic l-dopa fails to lessen rebound enhancement of self-stimulation after chronic haloperidol

    Pharmacol. Biochem. Behav.

    (1988)
  • P.E. Shreve et al.

    Role of quisqualic acid receptors in the hypermotility response produced by the injection of AMPA into the nucleus accumbens

    Pharmacol. Biochem. Behav.

    (1988)
  • R.F. Thompson

    The neural basis of basic associative learning of discrete behavioral responses

    Trends Neurosci.

    (1988)
  • S.F. Williams et al.

    Motivational vs motor effects of striatal and pallidal gabergic projections to subthalamic and entopeduncular nuclei, ventromedial thalamus, and ventral globus plallidus

    Pharmacol. Biochem. Behav.

    (1987)
  • R.A. Wise

    Catecholamine theories of reward: a critical review

    Brain Res.

    (1978)
  • M.A. Anis et al.

    The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N-methyl-d-aspartate

    Br. J. Pharmacol.

    (1983)
  • A. Artola et al.

    Long-term potentiation and NMDA receptors in rat visual cortex

    Nature

    (1987)
  • V.J. Balcar et al.

    Stereospecificity of the inhibition of l-glutamate and l-aspartate high affinity uptake in rat brain slices by threo-3-hydroxyaspartate

    J. Neurochem.

    (1977)
  • C. Bialajew et al.

    Behaviorally derived measures of conduction velocity in the substrate for rewarding medial forebrain bundle stimulation

    Brain Res.

    (1982)
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