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Effects of clonidine and α-adrenoceptor antagonists on motor activity in DSP4-treated mice I: Dose-, time- and parameter-dependency

Neurotoxicity Research volume 1, Article number: 235 (1999) Cite this article

Abstract

In three experiments the acute effects of clonidine administration upon locomotor and rearing behaviour of mice pretreated with the selective noradrenaline (NA) neurotoxin, DSP4 (1 X 75 mg/kg, i.p.) 10–12 days previously, were studied. Clonidine (0.01, 0.05, 0.25, 1.25 and 3.0 mg/kg, i.p.) induced a dose-dependent reduction of motor activity during the initial 30 min of testing in both DSP4-treated and control mice; this effect was attenuated by DSP4 treatment in the 0.01, 0.05, 0.25 and 3.0 mg/kg dose groups. By the third 30-min period of testing (60–90 min), each clonidine dose group, except the highest (3.0 mg/kg) dose for locomotion and the two highest (1.25 and 3.0 mg/kg) doses for rearing, induced increases in motor activity in the control mice. In DSP4-treated mice, a large increase in locomotor counts was produced by the 0.05 mg/kg dose of clonidine with lesser increases induced by the 0.01 mg/kg dose group, whereas a lesser effect of the 0.05 mg/kg group (30–60 min) was obtained for rearing but a larger effect of the 0.25 mg/kg group (60–90 min). Yohimbine (0.5 mg/kg, i.p., 15 min before clonidine) attenuated the suppressive effects of clonidine (0.01 and 0.05 mg/kg) during the initial 30 min of testing and markedly increased locomotor and rearing counts, both by itself and in combination with each dose of clonidine, in both DSP4-treated and control mice over the following 90 min of testing. Yohimbine treatment attenuated the large increase in locomotor counts induced by the 0.05 mg/kg dose of clonidine in the NA-denervated mice. Dihydroergotamine (0.5 mg/kg, i.p., 15 min before clonidine) did not antagonise either the initial suppressive effect or the later supersensitivity effect of the 0.05 mg/kg dose of clonidine. DSP4 treatment by itself reduced motor activity. The effects of clonidine, dose- and time-dependently, by itself or in coadministration with α-adrenoceptor antagonists, in DSP4-treated or control mice displayed denervation-induced supersensitivity that appear to reflect mainly postsynaptic α2-adrenoceptor mediation.

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Affiliations

  1. Department of Psychology, University of Göteborg, Box 500, SE-40530, Göteborg, Sweden

    Trevor Archer

  2. Department of Psychiatry and Neuroscience, University of Uppsala, Ulleråkers Hospital, S-75017, Uppsala, Sweden

    Anders Fredriksson

Authors
  1. Trevor Archer
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  2. Anders Fredriksson
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Correspondence to Trevor Archer.

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Archer, T., Fredriksson, A. Effects of clonidine and α-adrenoceptor antagonists on motor activity in DSP4-treated mice I: Dose-, time- and parameter-dependency. neurotox res 1, 235 (1999). https://doi.org/10.1007/BF03033254

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  • DOI: https://doi.org/10.1007/BF03033254

Keywords

  • DSP4
  • Control
  • Clonidine
  • Dose
  • Time
  • Parameter
  • Locomotion
  • Rearing
  • Potentiation
  • Co-administration
  • Yohimbine
  • Dihydroergotamine
  • Attenuate
  • Antagonise
  • Supersensitivity
  • Postsynaptic
  • α2-adrenoceptors
  • Mice