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Neurotoxicity Research

, 1:235 | Cite as

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

  • Trevor Archer
  • Anders Fredriksson
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.

Keywords

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

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Copyright information

© Springer 1999

Authors and Affiliations

  1. 1.Department of PsychologyUniversity of GöteborgGöteborgSweden
  2. 2.Department of Psychiatry and NeuroscienceUniversity of Uppsala, Ulleråkers HospitalS-75017UppsalaSweden

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