Electrophysiological effects of the enantiomers of 3-PPP on neurons in the locus coeruleus of the rat.
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.
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
D010880:Piperidines; D015016:Yohimbine; C026539:preclamol; D006220:Haloperidol; D011224:Prazosin