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Effects of clonidine and α-adrenoceptor antagonists on motor activity in DSP4-treated mice II: Interactions with apomorphine

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Abstract

Adult mice were administered either the noradrenaline (NA) neurotoxin, N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine, (DSP4), or distilled water (control), 10–12 days before motor activity testing, and 6 h before testing all the mice were administered reserpine (10mg/kg), the monoamine-depleting agent. The interactive effects of (I) clonidine, the α2-adrenoceptor agonist, with the dopamine (DA) agonist, apomorphine, and the α2-antagonist, yohimbine, and (II) with either yohimbine or the α1-antagonist, prazosin, upon motor behaviour in activity test chambers were studied in reserpinized DSP4-treated and control mice. It was shown that apomorphine (3mg/kg) increased locomotor and total activity in both reserpinized DSP4-treated and control mice but the effect was attenuated in the DSP4 mice. Coadministration of clonidine (3 mg/kg) with apomorphine potentiated the effects of apomorphine on motor activity and this effect was enhanced markedly by DSP4 pretreatment. Yohimbine (10 mg/kg) antagonised the motor activity-stimulating effects of apomorphine in both DSP4-treated and control mice. Co-administration of clonidine with apomorphine, following yohimbine, restored motor activity levels to those obtained in the absence of yohimbine and this effect upon locomotor activity was enhanced by DSP4 pretreatment. The effects of clonidine on motor activity were enhanced by NA-denervation. Prazosin (3 mg/kg) enhanced the locomotor activity of both reserpinized DSP4-treated and control mice after the initial 30-mm period but was not affected by DSP4 treatment. Analysis of post-decapitation convulsions (PDCs) indicated loss of the reflex by DSP4 pretreatment. Reserpine pretreatment abolished the initial, exploratory phase (30 min) of motor activity. These results demonstrate interactions between NA and DA systems that may bear eventual relevance to neurologic disorders such as parkinsonism.

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Authors and Affiliations

  1. Department of Psychiatry, University of Uppsala, Ulleråkers Hospital, S-75017, Uppsala, Sweden

    Anders Fredriksson

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

    Trevor Archer

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

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Fredriksson, A., Archer, T. Effects of clonidine and α-adrenoceptor antagonists on motor activity in DSP4-treated mice II: Interactions with apomorphine. neurotox res 1, 249–259 (1999). https://doi.org/10.1007/BF03033255

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