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Electrophysiological effects of the enantiomers of 3 3 hydroxyphenyl n n propylpiperidine on neurons in the locus coeruleus of the rat

, : Electrophysiological effects of the enantiomers of 3 3 hydroxyphenyl n n propylpiperidine on neurons in the locus coeruleus of the rat. Neuropharmacology 25(9): 1003-1008

Extracellular single unit and microiontophoretic studies were carried out in rats, anesthetized with chloral hydrate, to investigate the actions of the enantiomers of the dopamine (DA) agonist 3-(3-hydroxyphenyl)-N-n-propylpiperidine (3-PPP) on the firing rate of noradrenaline-containing neurons in the locus coeruleus (LC). Intravenously-administered (+)-3-PPP dose-dependently reduced firing of cells in the locus coeruleus with a 50% inhibition occurring after 2 mg/kg. This action was partially antagonized by the alpha2-noradrenaline (NA) antagonist, yohimbine, but not by the DA antagonist haloperidol or the alpha1-antagonist prazosin. Pretreatment with reserpine completely blocked the suppressant effect of (+)-3-PPP on firing rate. Iontophoretically-applied (+)-3-PPP did not influence the basal firing rate of cells in the locus coeruleus and failed to influence the inhibitory action of simultaneously-applied DA. Neither intravenously nor iontophoretically administered (-)-3-PPP influenced basal firing rate of neurones in the locus coeruleus. However, intravenously-administered drug weakly reversed the inhibitory action of the alpha2-agonist clonidine (100 .mu.g/kg) and iontophoretic ejection antagonized the inhibitory action of DA. These findings suggest that (-)-3-PPP possesses a weak antagonist action at alpha2-adrenoceptors present in the locus coeruleus. In contrast, administration of (+)-3-PPP resulted in a weak activation of these receptors which was possibly the result of an enhanced release of NA.

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