α-Noradrenergic modulation of hypothalamic self-stimulation: Studies employing clonidine, 1-phenylephrine and α-methyl-p-tyrosine

  • Hunt G
  • Atrens D
  • Chesher G
 et al. 
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Abstract

An α-noradrenergic substrate of rewarding intracranial stimulation (ICS) has been hypothesized based on the observation that the α-antagonist phentolamine produced an inhibition of self-stimulation. The present experiment investigated the effects on hypothalamic self-stimulation of the alpha agonist clonidine in normal and in catecholamine-depleted rats. Using a shuttle-box technique that provides a rate-independent index of the rewarding and aversive components of ICS, it was demonstrated that clonidine produces a dose-dependent inhibition of reward that is clearly dissociable from any non-specific effects of the drug. The ineffectiveness of the peripheral α-agonist 1-phenylephrine indicates that the inhibition of reward produced by clonidine is mediated centrally. Clonidine and the catecholamine synthesis inhibitor α-methyl-p-tyrosine act together in a synergistic manner to greatly increase the magnitude and prolong the duration of the inhibition of reward while leaving the aversive component unaffected. These data are interpreted as supporting an α-noradrenergic basis of ICS reward while indicating that the aversive component of ICS is essentially independent of noradrenergic transmission. © 1976.

Author-supplied keywords

  • 1-Phenylephrine
  • Aversion
  • Catecholamines
  • Clonidine
  • Noradrenaline
  • Reward
  • Self-stimulation
  • Synergism
  • α-Methyl-p-tyrosine
  • α-Receptors

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Authors

  • Glenn HuntDiscipline of Psychiatry, University of Sydney

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  • Dale M. Atrens

  • Gregory B. Chesher

  • Frederick T. Becker

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