Skip to main content

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

Neurotoxicity Research volume 1, Article number: 249 (1999) Cite this article

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.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

43,34 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

Reference

  • Archer, T., Cotic, T. and Jarbe, T.U.C. (1982) Attenuation of the context effect and lack of unconditioned stimulus preexposure effect in taste-aversion learning following treatment with DSP4, the selective noradrenaline neurotoxin. Behav. Neural Biol,35, 159–173.

    PubMed  Article  CAS  Google Scholar 

  • Archer, T., Jonsson, G. and Ross, S.B. (1984) A parametric study of the effects of the noradrenaline neurotoxin DSP4 on avoidance acquisition and noradrenaline neurones in the CNS of the rat. Br.J. Pharmacol,82, 249–257.

    PubMed  CAS  Google Scholar 

  • Archer, T., Jonsson, G. and Ross, S.B. (1985) Active and passive avoidance following the administration of systemic DSP4, xylamine, or p-chloroamphetamine. Behav. Neural Biol,43, 238–249.

    PubMed  Article  CAS  Google Scholar 

  • Archer, T., Fredriksson, A., Jonsson, G., Lewander, T., Mohammed, A.K., Ross, S.B. and Soderberg, U. (1986) Central noradrenaline depletion antagonizes aspects of d-amphetamine-induced hyperactivity in the rat. Psychopharmacology (Berl.)88, 141–146.

    Article  CAS  Google Scholar 

  • Berlan, M., Rascol, O.et al. (1989) Alpha 2-adrenergic sensitivity in Parkinson’s disease. Clin. Neuropharmacol,12, 138–144.

    PubMed  Article  CAS  Google Scholar 

  • Biaggioni, I., Robertson, R.M. and Robertson, D. (1994) Manipulation of norepinephrine metabolism with yohimbine in the treatment of autonomic failure. J. Clin. Pharmacol,34, 418–423.

    PubMed  CAS  Google Scholar 

  • Carlsson, M. and Carlsson, A. (1989) Dramatic synergism between MK-801 and clonidine with respect to locomotor stimulatory effect in monoamine-depleted mice. J. Neural Transm.77, 65–71.

    PubMed  Article  CAS  Google Scholar 

  • Carlsson, M. and Svensson, A. (1990a) Interfering with glutamatergic neurotransmission by means of NMDA antagonist administration discloses the locomotor stimulatory potential of other transmitter systems. Pharmacol. Biochem. Behav.,36, 45–50.

    PubMed  Article  CAS  Google Scholar 

  • Carlsson, M. and Svensson, A. (1990b) The non-competitive NMDA antagonists MK-801 and PCP, as well as the competitive NMDA antagonist SDZ EAA494 (D-CPPene), interact synergistically with clonidine to promote locomotion in monoamine-depleted mice. Life Sci.,47, 1729–1736.

    PubMed  Article  CAS  Google Scholar 

  • Carlsson, M., Svensson, A. and Carlsson, A. (1991) Synergistic interactions between muscarinic antagonists, adrenergic agonists and NMDA antagonists with respect to locomotor stimulatory effects in monoamine-depleted mice. Naunyn-Schmiedeberg’s Arch. Pharmacol,343, 568–573.

    Article  CAS  Google Scholar 

  • Cash, R., Ruberg, M.et al. (1984) Adrenergic receptors in Parkinson’s disease. Brain Res.,322, 269–275.

    PubMed  Article  CAS  Google Scholar 

  • Chopin, P., Pellow, S. and File, S.E. (1986) The effects of yohimbine on exploratory and locomotor behaviour are attributable to its effects at noradrenaline and not at benzodiazepine receptors. Neuropharmacology,25, 53–57.

    PubMed  Article  CAS  Google Scholar 

  • Cristofol, R.M. and Rodriquez-Farre, E. (1991) Differential presynaptic effects of hexachlorocyclohexane isomers on noradrenaline release in cerebral cortex. Life Sci.,49, 1111–1119.

    PubMed  Article  CAS  Google Scholar 

  • Dolphin, A.C., Jenner, P.et al. (1976) The relative importance of dopamine and noradrenaline receptor stimulation for the restoration of motor activity in reserpine or alpha-methyl-p-tyrosine pre-treated mice. Pharmacol. Biochem. Behav.,4, 661–670.

    PubMed  Article  CAS  Google Scholar 

  • Eshel, G., Ross, S.B. et al (1990) Alpha Kbut not alpha 2)-adrenoceptor agonists in combination with the dopamine D2 agonist quinpirole produce locomotor stimulation in dopamine-depleted mice. Pharmacol. Toxicol,67, 123–131.

    PubMed  CAS  Article  Google Scholar 

  • Fornai, F., Bassi, L., Torracca, M.T., Alessandri, M.G., Scalori, V. and Corsini, G.U. (1996) Region- and neurotransmitter-dependent species and strain differences in DSP4-induced monoamine depletion in rodents. Neurodegeneration,5, 241–249.

    PubMed  Article  CAS  Google Scholar 

  • Fornai, R, Alessandri, M.G., Torracca, M.T., Bassi, L. and Corsini, G.U. (1997) Effects of noradrenergic lesions on MPTP/MPP+ kinetics and MPTP-induced nigrostriatal dopamine depletions. J. Pharmacol. Exp. Ther.,283, 100–107.

    PubMed  CAS  Google Scholar 

  • Fornai, P., Alessandri, M.G., Torracca, M.T., Bassi, L., Scatori, V. and Corsini, G.U. (1998a) Noradrenergic modulation of methampetamine-induced striatal dopamine depletion. Ann NY Acad. Set.,844, 166–177.

    Article  CAS  Google Scholar 

  • Fornai, R, Bassi, L., Torracca, M.T., Alessandri, M.G., Scatori, V. and Corsini, G.U. (1998b) Regional- and neurotransmitter-dependent species and strain differences in DSP4-induced monoamine depletion in rodents. Neurodegeneration,5, 241–249.

    Article  Google Scholar 

  • Fornai, R, Giorgi, F.S., Alessandri, M.G., Giusiani, M. and Corsini, G.U. (1999) Effects of pretreatment with N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) on methamphetamine pharmacokinetics and striatal dopamine losses. J. Neurochem.,72, 777–784.

    PubMed  Article  CAS  Google Scholar 

  • Fredriksson, A. and Archer, T. (1994) MPTP-induced behavioural and biochemical deficits: A parametric analysis. J. Neural Transm.,7, 123–132.

    Article  CAS  Google Scholar 

  • Gobbi, M., Frittoli, E. and Mennini, T. (1990) The modulation of [3H]noradrenaline and [3H]serotonin release from rat brain synaptosomes is not mediated by the alpha 2B-adrenoceptor subtype. Naunyn Schmiedebergs Arch. Pharmacol.,342, 382–386.

    PubMed  Article  CAS  Google Scholar 

  • Gobbi, M., Frittoli, E. and Mennini, T. (1993) Further studies on alpha 2-adrenoceptor subtypes involved in the modulation of [3H]noradrenaline and [3H]5-hydroxytryptamine release from rat brain cortex synaptosomes. J. Pharm. Pharmacol,45, 811–814.

    PubMed  CAS  Google Scholar 

  • Goldstein, M., Engel, J.et al. (1983) Therapeutic potentials of centrally acting dopamine and alpha 2-adrenoceptor agonists. J. Neural Transm.,18(Suppl.) 257–263.

    CAS  Google Scholar 

  • Henry, B., Crossman, A.R.et al. (1998) Characterization of enhanced behavioural responses to L-DOPA following repeated administration in the 6-hydroxydopaminelesioned rat model of Parkinson’s disease. Exp. Neurol.,151, 334–342.

    PubMed  Article  CAS  Google Scholar 

  • Jonsson, G. (1980) Chemical neurotoxins as denervation tools in neurobiology. Annu. Rev. Neurosci.,3, 169–187.

    PubMed  Article  CAS  Google Scholar 

  • Jonsson, G. and Hallman, H. (1982) Response of central monoamine neurons following an early neurotoxic lesion. Bibl. Anal,23, 76–92.

    Google Scholar 

  • Jonsson, G., Hallman, H., Ponzio, F. and Ross, S.B. (1981) DSP4 (N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine) — a useful denervation tool for central and peripheral noradrenaline neurons. Eur. J. Pharmacol.,72, 173–188.

    PubMed  Article  CAS  Google Scholar 

  • Jonsson, G., Hallman, H. and Sundstrom, E. (1982) Effects of the noradrenaline neurotoxin DSP4 on the postnatal development of central noradrenaline neurons in the rat. Neuroscience,7, 2895–2907.

    PubMed  Article  CAS  Google Scholar 

  • Kirk, R.E. (1995) Experimental Design. Procedures in Behavioural Science. Belmont CA, Brooks/Cole Inc.

    Google Scholar 

  • Kiss, J.P, Zsilla, G., Mike, A., Zelles, T., Toth, E., Lajtha, A. and Vizi, E.S. (1995) Subtype-specificity of the presynaptic alpha 2-adrenoceptors modulating hippocampal norepinephrine release in rat. Brain Res.,674, 238–244.

    PubMed  Article  CAS  Google Scholar 

  • Kostowski, W. and Malatynska, E. (1983) Antagonism of behavioural depression produced by clonidine in the mongolian gerbil: A potential screening test for antidepressant drugs. Psychopharmacology,79, 203–208.

    PubMed  Article  CAS  Google Scholar 

  • Kunchandy, J. and Kulkarni, S.K. (1986) Reversal by alpha-2 agonists of diazepam withdrawal hyperactivity in rats. Psychopharmacology,90, 198–202.

    PubMed  Article  CAS  Google Scholar 

  • Limberger, N., Spath, L. and Starke, K. (1991) Subclassification of the presynaptic alpha 2-autoreceptors in rabbit brain cortex. Br. J. Pharmacol,103, 1251–1255.

    PubMed  CAS  Google Scholar 

  • Marien, M., Briley, M. and Colpaert, R (1993) Noradrenaline depletion exacerbates MPTP-induced striatal dopamine loss in mice. Eur. J. Pharmacol,236, 487–489.

    PubMed  Article  CAS  Google Scholar 

  • Mason, S.T. and Fibiger, H.C. (1979) Physiological function of descending noradrenaline projections to the spinal cord: Role in post-decapitation convulsions. Eur. J. Pharmacol,57, 29–34.

    PubMed  Article  CAS  Google Scholar 

  • Meana, J.J., Herrerra-Marschitz, M., Goiny, M. and Silveira, R. (1997) Modulation of catecholamine release by alpha 2-adrenoceptors and Il-imidazoline receptors in the rat brain. Brain Res.,744, 216–226.

    PubMed  Article  CAS  Google Scholar 

  • Musso, N.R., Gianrossi, R., Vergassola, C, Pende, A., Loverno, A., Galbariggi, G. and Lotti, G. (1992) Norepinephrine-induced plasma dopamine decrease in man: Pharmacological evidence of the involvement of alpha 2-adrenoceptors. J. Hypertens.,10, 1017–1023.

    PubMed  Article  CAS  Google Scholar 

  • Nishikawa, T, Tanaka, M., Tsuda, A., Kohno, Y. and Nagasaki, N. (1983) Differential effects of clonidine on alpha 1- and alpha 2-adrenoceptors in footshock-induced jumping behavior. Eur. J. Pharmacol,88, 399–401.

    PubMed  Article  CAS  Google Scholar 

  • Ogren, S.O., Archer, T. and Johansson, C. (1983) Evidence for a selective brain noradrenergic involvement in the locomotor stimulant effects of amphetamine in the rat. Neurosci. Lett.,43, 327–331.

    PubMed  Article  CAS  Google Scholar 

  • Ogren, S.O. and Goldstein, M. (1994) Phencyclidine and dizocilpine-induced hyperlocomotion are differently mediated. Neuropsychopharmacology,11, 167–177.

    PubMed  Article  CAS  Google Scholar 

  • Pucilowski, O., Trzaskowska, E., Kostowski, W. and Valzelli, L. (1987) Norepinephrine-mediated suppression of apomorphine-induced aggression and locomotor activity in the rat amygdala. Pharmacol Biochem. Behav.,26, 217–222.

    PubMed  Article  CAS  Google Scholar 

  • Riekkinen, M., Kejonen, K.et al. (1998) Reduction of noradrenaline impairs attention and dopamine depletion slows responses in Parkinson’s disease. Eur. J. Neurosci.,10, 1429–1435.

    PubMed  Article  CAS  Google Scholar 

  • Roberts, D.C.S., Mason, S.T. and Fibiger, H.C. (1978) Selective depletion of spinal noradrenaline abolishes post-decapitation convulsions. Life Sci.,23, 2411–2414.

    PubMed  Article  CAS  Google Scholar 

  • Ross, S.B. (1976) Long-term effects of N-2-chloroethyl-N-ethyl-2-bromobenzylamine hydrochloride on noradrenergic neurons in the rat brain and heart. Br. J. Pharmacol,58, 521–527.

    PubMed  CAS  Google Scholar 

  • Ross, S.B. and Renyi, L. (1976) On the long-lasting inhibitory effect of N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4) on the active uptake of noradrenaline. J. Pharm. Pharmacol,28, 458–459.

    PubMed  CAS  Google Scholar 

  • Sanchez-Merino, J.A., Arribas, S., Arranz, A., Mann, J. and Balfagon, G. (1990) Regulation of noradrenaline release in human cerebral arteries via presynaptic alpha 2-adrenoceptors. Gen. Pharmacol,21, 859–862.

    PubMed  CAS  Google Scholar 

  • Schmidt, W.J. (1994) Behavioural effects of NMDA-receptor antagonists. J. Neural Transm.,43(Suppl.), 63–69.

    CAS  Google Scholar 

  • Shoulson, Y. and Chase, T.N. (1976) Clonidine and the antiparkinsonian response to L-Dopa or piribedil. Neuropharmacology,15, 25–27.

    PubMed  Article  CAS  Google Scholar 

  • Starr, M.S. and Starr, B.S. (1994) Potentiation of dopaminedependent locomotion by clonidine in reserpine-treated mice is restricted to D2 agonists. J. Neural Transm.: PD and D sect.,7, 133–142.

    Article  CAS  Google Scholar 

  • Tarsy, D., Parkes, J.D.,et al. (1975) Clonidine in Parkinson’s disease. Arch. Neurol,32, 134–136.

    PubMed  CAS  Google Scholar 

Download references

Author information

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

Authors
  1. Anders Fredriksson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Trevor Archer
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Trevor Archer.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

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 (1999). https://doi.org/10.1007/BF03033255

Download citation

  • Revised:

  • DOI: https://doi.org/10.1007/BF03033255

Keywords

  • DSP4
  • Control
  • Reserpine
  • Locomotion
  • Total activity
  • Clonidine
  • Apomorphine
  • Co-administration
  • Enhancement
  • Yohimbine
  • Antagonism
  • Prazosin
  • Supersensitivity
  • Attenuation
  • PDCs
  • Movement disorders
  • Mice