Functional supersensitivity to adrenergic agonists in the rat after DSP-4, a selective noradrenergic neurotoxin

Psychopharmacology (Berl). 1983;81(1):1-5. doi: 10.1007/BF00439263.

Abstract

Rats treated with DSP-4 [N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine], a selective noradrenergic neurotoxin, showed no differences compared to control rats in the number of head dips, a measure of exploratory behavior. Since a previous neurochemical investigation had demonstrated that DSP-4 rats have supersensitive alpha 2- and beta-adrenergic receptors in certain regions of the central nervous system, the behavior of these animals was also examined after the injection of clonidine, an alpha 2 agonist, and clenbuterol, a beta agonist. These drugs reduced, in a dose-dependent manner, the head-dipping of both control and DSP-4 rats. However, this effect was of greater magnitude in DSP-4 animals. Control experiments suggested that the response to clonidine and clenbuterol was mediated centrally by alpha 2 and beta receptors, respectively. Other behavioral experiments with agonists of the dopaminergic and serotoninergic systems indicated that these neurotransmitter systems were unchanged in DSP-4 animals. The results are discussed in terms of the selective action of DSP-4 and the responsiveness of DSP-4 rats to adrenergic agonists. The DSP-4-treated rat may constitute a new model of functional supersensitivity to adrenergic agonists.

MeSH terms

  • Amines / pharmacology*
  • Animals
  • Behavior, Animal / drug effects
  • Benzylamines / pharmacology*
  • Clenbuterol / pharmacology
  • Clonidine / pharmacology
  • Exploratory Behavior / drug effects
  • Hemodynamics / drug effects
  • Male
  • Microsomes, Liver / metabolism
  • Myocardial Contraction / drug effects
  • Neurotoxins / pharmacology*
  • Norepinephrine / physiology*
  • Rats
  • Receptors, Dopamine / drug effects
  • Receptors, Serotonin / drug effects
  • Sympathomimetics / pharmacology*

Substances

  • Amines
  • Benzylamines
  • Neurotoxins
  • Receptors, Dopamine
  • Receptors, Serotonin
  • Sympathomimetics
  • Clonidine
  • DSP 4
  • Norepinephrine
  • Clenbuterol