Actions of phencyclidine on rat locus coeruleus neurones in vitro.
Neuroscience February 1986 DOI: 10.1016/0306-4522(86)90261-7 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | In vitro electrophysiological study Peer reviewed |
|---|---|
| Population | Neurons in the rat locus coeruleus brain slice |
| Interventions | Phencyclidine (+)-1-(1-phenylcyclohexyl)-3-methyl piperidine (+/-)-N-allyl-N-normetazocine N-methyl-D-aspartic acid noradrenaline desmethylimipramine [D-Ala2 MePhe4 Gly-ol5]enkephalin |
| Key points | Phencyclidine depressed N-methyl-D-aspartic acid responses most potently (IC50 0.4 microM) and was the only effect showing stereoselectivity; noradrenaline and enkephalin responses were less sensitive, and action potential prolongation required high concentrations. No effects were seen on membrane potential, input resistance, or spontaneous firing. The authors suggest these actions may contribute to the phencyclidine behavioral syndrome. |
Abstract
Intracellular recordings were made from neurones in the rat locus coeruleus in a brain slice maintained in vitro. Phencyclidine and related psychotomimetic drugs, applied in known concentrations in the fluid bathing the slice, depressed responses to N-methyl-D-aspartic acid noradrenaline (in the presence of the uptake inhibitor desmethylimipramine) and [D-Ala2,MePhe4,Gly-ol5]enkephalin and also prolonged the action potential. The sensitivities of these responses to depression by phencyclidine was N-methyl-D-aspartic acid (IC50 0.4 microM) greater than noradrenaline (IC50 3.9 microM) greater than [D-Ala2,MePhe4,Gly-ol5]enkephalin (IC50 8.5 microM) greater than prolongation of the action potential (41% increase by 30 microM). Stereoselectivity was observed only in the depression of responses to N-methyl-D-aspartic acid where (+)-1-(1-phenylcyclohexyl)-3-methyl piperidine was 3.3-fold more potent in suppressing N-methyl-D-aspartic acid depolarizations than its (-) isomer. The responses to N-methyl-D-aspartic acid were also depressed by the structurally unrelated psychotomimetic (+/-)-N-allyl-N-normetazocine (IC50 0.9 microM). All of the effects of the psychotomimetic drugs examined were slow in onset and difficult to reverse following washout. No effect of phencyclidine (0.03-100 microM) or related drugs was observed on membrane potential, input resistance or spontaneous action potential firing rate of locus coeruleus neurones. The depression of responses to N-methyl-D-aspartic acid by phencyclidine was the most potent and the only stereoselective effect of those studied. The importance of this effect and of those not showing stereoselectivity in relation to the phencyclidine behavioural syndrome is discussed.