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The interaction of clonidine with dopamine-dependent behaviour in rodents

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Summary

The effect of clonidine on a number of behavioural parameters believed to be expressed through central dopaminergic mechanisms has been studied in rodents.

  1. 1.

    Clonidine (0.06–2 mg/kg) potentiated the circling response to standard doses of both apomorphine (0.25 mg/kg) and amphetamine (3 mg/kg) in mice with unilateral destruction of nigro-neostriatal dopamine nerve terminals. Similarly, clonidine (0.06–2 mg/kg) enhanced the locomotor effect of apomorphine in reserpinised mice.

  2. 2.

    Clonidine (0.5 mg/kg) was without effect on the patterns of stereotyped behaviours induced by the dopamine agonist apomorphine (0.1–5 mg/kg) in the rat. Unilateral intrastriatal injections of clonidine (5–100 μg) caused no discernable behavioural effects in rats.

  3. 3.

    Injection of apomorphine (10 μg) bilaterally into the region of the nucleus accumbens of the rat resulted in a hyperactive response, while bilateral injection of clonidine (50 μg) into this region caused marked sedation, thus mimicking the effects of these drugs on motor activity when administered systemically. Combinations of systemic or nucleus accumbens apomorphine and clonidine resulted in potentiated stereotypy and prolonged hyperactivity responses.

  4. 4.

    Clonidine (0.5 mg/kg) potentiated the cataleptic effect of the dopamine antagonist haloperidol (0.1–2 mg/kg) in rats.

Clonidine therefore potentiated those behavioural responses exhibiting a locomotor component (viz. circling and hyperactivity), but was without effect on stereotypy. The potentiation of catalepsy induced by clonidine may be explained in non-specific sedatory terms.

It is apparent that clonidine acts through a secondary neurone system which modifies the effects of dopamine receptor stimulation, although the exact site of this interaction is not clear. The tentative conclusion might be that clonidine inhibits 5-HT neuronal activity, and the possible relationships between 5-HT and NA and dopamine are discussed.

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Author notes

  1. C. J. Pycock

    Present address: Department of Pharmacology, The Medical School, University of Bristol, BS8 1TD, Bristol, UK

Authors and Affiliations

  1. University Department of Neurology, Institute of Psychiatry and King's College Hospital Medical School, Denmark Hill, SE5 8AF, London, UK

    C. J. Pycock, P. G. Jenner & C. D. Marsden

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  1. C. J. Pycock
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  2. P. G. Jenner
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  3. C. D. Marsden
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Pycock, C.J., Jenner, P.G. & Marsden, C.D. The interaction of clonidine with dopamine-dependent behaviour in rodents. Naunyn-Schmiedeberg's Arch. Pharmacol. 297, 133–141 (1977). https://doi.org/10.1007/BF00499922

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  • DOI: https://doi.org/10.1007/BF00499922

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