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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Allgaier, C, Agneter, E., Feuerstein, T.J. and Singer, E.A. (1992) Estimation of the biophase concentration of noradrenaline at presynaptic alpha 2-adrenoceptors in brain slices. Naunyn Schmiedebergs Arch. Pharmacol.345, 402–409.
Allgaier, C, Hertting, G. and Singer, E.A. (1991) A detailed study on the effects of protein kinase C activation on alpha-2 adrenoceptor-coupled modulation of norephinephrine release in hippocampus. J. Pharmacol. Exp. Ther.258, 143–148.
Anden, N.-E., Corrodi, H., Fuxe, K., Hokfelt, B., Hokfelt, T., Rydin, C. and Svensson, T. (1970) Evidence for a central noradrenaline stimulation by clonidine. Life Sci.9, 513–523.
Archer, T., Cotic, T. and Jarbe, T.U.C. (1982a) 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.
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.
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.
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.
Archer, T., Mohammed, A.K., Ross, S.B. and Soderberg, U. (1983) T-maze learning, spontaneous activity and food intake recovery following systemic administration of the noradrenaline neurotoxin, DSP4. Pharmacol. Biochem. Behav.19, 121–130.
Archer, T., Ogren, S.O., Johansson, G. and Ross, S.B. (1982b) DSP4-induced two-way active avoidance impairment in rats: involvement of central and not peripheral noradrenaline depletion. Psychopharmacology76, 303–309.
Asin, K.E., Wirtshafter, D. and Fibiger, H.C. (1982) Alterations in drug induced catalepsy and post-decapitation convulsions following brain and spinal cord depletion of norepinephrine by the neurotoxin DSP-4. Life Sci.30, 1531–1536.
Berridge, C.W. and Dunn, A.J. (1990) DSP-4-induced depletion of brain norepinephrine produces opposite effects on exploratory behavior 3 and 14 days after treatment. Psychopharmacology100, 504–508.
Danysz, W., Jonsson, G., Mohammed, A.K. and Archer, T. (1985) The hindlimb extensor reflex is not a reliable marker of post-decapitation convulsions or spinal noradrenaline depletion in rats. Eur.J. Pharmacol.116, 331–333.
Dooley, DJ., Bittiger, H., Hauser, K.L., Bischoff, S.L. and Waldmeier, PC. (1983a) Alteration of central alpha 2- and beta-adrenergic receptors in the rat after DSP4, a selective noradrenergic neurotoxin. Neuroscience9, 889–898.
Dooley, D.J., Mogilnicka, E., Delini-Stula, A., Waechter, R, Truog, A. and Wood, J. (1983b) Functional supersensitivity to adrenergic agoinists in the rat after DSP-4, a selective noradrenergic neurotoxin. Psychopharmacology81, 1–5.
Du, X.J. and Riersmersma, R.A. (1992) Effects of presynaptic alpha-adrenoceptors and neuronal reuptake on noradrenaline overflow and cardiac response. Eur. J. Pharmacol.211, 221–226.
Fornai, F., Bassi, L., Toracca, M.T., Alessandri, M.G., Scalori, V. and Corsini, G.U. (1996) Region- and neurotransmitterdependent species and strain differences in DSP-4-induced monoamine depletion in rodents. Neurodegeneration5, 241–249.
Forray, M.I., Bustos, G. and Gysling, K. (1997) Regulation of norepinephrine release from the rat bed nucleus of the stria terminalis: in vivo microdialysis studies. J. Neurosci. Res.50, 1040–1046.
Fredriksson, A. and Archer, T. (1994) MPTP-induced behavioural and biochemical deficits: a parametric analysis. J. Neural. Transm.7, 123–132.
Haeusler, G. (1973) Activation of the central pathway of the baroreceptor reflex, a possible mechanism of the hypotensive action of clonidine. Naunyn-Schmiedeberg’s Arch. Pharmacol.85, 1–14.
Jonsson, G. (1980) Chemical neurotoxins as denervation tools in neurobiology. Annu. Rev. Neurosci.3, 169–187.
Jonsson, G. and Hallman, H. (1982) Response of central monoamine neurons following an early neurotoxic lesion. Bibl. Anat.23, 76–92.
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. Eut. J. Pharmacol.72, 173–188.
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. Neuroscience7, 2895–2907.
Kirk, R.E. (1995) Experimental Design. Procedures in Behavioural Science. Belmont CA, Brooks/Cole Inc.
Kobinger, W. and Pichler, W. (1975) The central modulatory effect of clonidine on the cardiodepressor reflex after suppression of synthesis and storage of noradrenaline. Eur. J. Pharmacol.30, 56–62.
Lerner, U. and Larsson, A. (1984) Differential sensitivity of pinna reflex and esophageal temperature to clonidine in mice depleted of central noradrenaline by DSP4. Experientia40, 963–965.
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.
Minor, B.G., Danysz, W., Jonsson, G., Mohammed, A.K., Post, C. and Archer, T. (1989) Adaptive changes in alpha-2 adrenoceptor mediated responses: analgesia, hypothermia and hypoactivity. Pharmacol. Toxicol.65, 143–151.
Monti, J.M., D’Angelo, L., Jantos, H., Barbeito, L. and Abo, V. (1988) Effect of DSP-4, a noradrenergic neurotoxin, on sleep and wakefulness and sensitivity to drugs acting on adrenergic receptors in the rat. Sleep11, 370–377.
Ponzio, E, Hallman, H. and Jonsson, G. (1981) Noradrenaline and dopamine interaction in rat brain during development. Med. Biol.59, 161–169.
Post, C., Arwestrom, E., Minor, B.G., Wikberg, E., Jonsson, G. and Archer, T. (1985) Noradrenaline depletion increases noradrenaline-induced antinociception in mice. Neurosci. Lett.59, 105–109.
Post, C., Persson, M.L., Archer, T., Minor, B.G., Danysz, W. and Sundstrom E. (1987) Increased antinociception by alphaadrenoceptor drugs after spinal cord noradrenaline depletion. Eur. J. Pharmacol.137, 107–116.
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.
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.
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.
Silberstein, S.D. (1997) The pharmacology of ergotamine and dihydroergotamine. Headache37(Suppl. 1), S15-S25.
Spyraki, C. and Fibiger, H.C. (1982) Clonidine-induced sedation in rats: evidence for mediation by postsynaptic alpha 2-adrenoreceptors. J. Neural Transm.54, 153–163.
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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, 235–247 (1999). https://doi.org/10.1007/BF03033254
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DOI: https://doi.org/10.1007/BF03033254