title: Electrophysiological effects of the enantiomers of 3-PPP on neurons in the locus coeruleus of the rat.
abstract: 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 alpha 2-noradrenaline (NA) antagonist, yohimbine, but not by the DA antagonist haloperidol or the alpha 1-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 alpha 2-agonist clonidine (100 micrograms/kg) and iontophoretic ejection antagonized the inhibitory action of DA. These findings suggest that (-)-3-PPP possesses a weak antagonist action at alpha 2-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.
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D006220:Haloperidol / Q000494:pharmacology; D007275:Injections, Intravenous; D007478:Iontophoresis; D008125:Locus Coeruleus / Q000166:cytology* / Q000187:drug effects; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology*; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013237:Stereoisomerism; D015016:Yohimbine / Q000494:pharmacology
chemical_list: D010880:Piperidines; D015016:Yohimbine; C026539:preclamol; D006220:Haloperidol; D011224:Prazosin