Abstract
NORADRENERGIC neurones of the locus coeruleus (LC; A6 of ref. 1) are inhibited by the systemic or local administration of adrenergic agonists2–5, opiates6,7 and enkephalins8,9. The adrenergic receptors of the LC, which are of the presynaptic or α2 type5, seem to mediate inhibitory responses to recurrent LC collaterals10 and adrenaline inputs from the lower brain stem4,11. In addition to adrenergic receptors, there are opiate receptors located in the LC12,13 which presumably mediate the actions of endogenous opiate-like substances (enkephalins and β-endorphin) located in nerve terminals within the LC14–16. Recently, clonidine, which is the most powerful of the α2 agonists known to inhibit the firing of LC neurones3,5, has been reported to suppress the symptoms of opiate withdrawal in humans17. On this basis, the latter authors suggested that the opiate-withdrawal syndrome may be due in part to increased noradrenergic neuronal activity in areas such as the LC which are regulated by both α2 adrenoceptors and opiate receptors. In this connection, it is interesting that the drug piperoxane, which blocks α2 adrenoceptors and accelerates the firing of LC neurones4,5 produces many of the symptoms (such as anxiety and hypertension) seen in opiate withdrawal18. In the present study, single-cell recording and microiontophoretic techniques were used to establish the development of tolerance of LC cells to the depressant effects of morphine, naloxone-induced withdrawal activations of LC neuronal firing in morphine-dependent animals, and the ability of clonidine to suppress the withdrawal of LC neurones through a non-opiate receptor.
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AGHAJANIAN, G. Tolerance of locus coeruleus neurones to morphine and suppression of withdrawal response by clonidine. Nature 276, 186–188 (1978). https://doi.org/10.1038/276186a0
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DOI: https://doi.org/10.1038/276186a0
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