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Functional evidence for postsynaptic supersensitivity of central noradrenergic receptors after denervation

Naturevolume 256pages659661 (1975) | Download Citation

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Abstract

THE development of postsynaptic or postjunctional supersensitivity in peripheral, noradrenergically innervated tissue after deafferentation has been clearly demonstrated1–3. In addition there exists considerable functional and biochemical evidence that central dopaminergic receptors in the neostriatum become supersensitive after lesions of the nigro-neostriatal projection4–8. Neurochemical evidence has been provided which is consistent with the development of postjunctional supersensitivity of central noradrenoceptors after deafferentation. Thus after intraventricular injections of 6-hydroxydopamine (6-OHDA), a neurotoxin for catecholaminergic neurones, noradrenaline (NA) stimulated synthesis of cyclic AMP is potentiated9–11. Functional evidence for the development of this type of supersensitivity in central NA receptors is, however, lacking. An enhanced response to intracisternally administered α-methylnoradrenaline in 6-OHDA pretreated rats has been reported12 but such an effect could be mediated by changes in either pre- or postsynaptic mechanisms. Our experiments were designed to provide functional confirmation for the presence of postjunctional supersensitivity in central noradrenoceptors after lesions of central noradrenergic neurones. Clonidine [2-(2,6-dichlorophenylamino)-2-imidazoline] is a directly acting α-NA receptor agonist13–15 and has been shown to lower body temperature by a central α-noradrenergic mechanism. Thus intraperitoneal, intracisternal or intrahypothalamic injections of clonidine decrease body temperature16,17. It was hypothesised that if central noradrenoceptive neurones become supersensitive after destruction of noradrenergic afferents by 6-OHDA, then clonidine-induced hypothermia should be potentiated in lesioned animals.

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  1. Division of Neurological Sciences, Department of Psychiatry, University of British Columbia, Vancouver, Canada, V6T 1W5

    • A. P. ZIS
    •  & H. C. FIBIGER

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https://doi.org/10.1038/256659a0

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