Different capability of N-methyl-D-aspartate antagonists to elicit EEG and behavioural phencyclidine-like effects in rats.
S Sagratella, A Pezzola, P Popoli, A S Scotti de Carolis
Psychopharmacology 1992 DOI: 10.1007/bf02245874 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical comparative study Peer reviewed |
|---|---|
| Population | Rats |
| Interventions | Phencyclidine (PCP) dizocilpine (MK 801) dextromethorphan (DM) SL 82.0715 CPP CGS 19755 |
| Dose | up to 100 mg/kg IP for dextromethorphan and SL 82.0715 |
| Key points | The NMDA antagonists MK 801, CGS 19755, and CPP produced PCP-like EEG stages 1-3 and PCP-like behaviors in rats, with potency ranking MK 801 > PCP > CGS 19755 > CPP. Dextromethorphan and SL 82.0715, up to 100 mg/kg IP, produced only stage 1 EEG changes and no PCP-like behaviors. The authors argue this strongly suggests NMDA neurotransmission is involved in PCP's behavioral and EEG effects. |
Abstract
Phencyclidine (PCP), a drug inducing schizophrenia-like symptoms in humans, is reported to be a non-competitive antagonist at the N-methyl-D-aspartate (NMDA) subtype of excitatory amino acid receptors. In rats, PCP produces three dose-dependent stages of EEG patterns: 1) increase of cortical desynchronization duration; 2) increase of the amplitude of the high-frequency (20-30 Hz) low-voltage (30-50 microV) cortical background activity; 3) appearance of cortical slow (2-3 Hz) wave-sharp wave complexes. These EEG changes are accompanied by stimulatory-depressive effects such as stereotypy (circling, head weaving) and ataxia. In the present study, the EEG and behavioural effects induced by systemic administration of the NMDA antagonists dizocilpine (MK 801), dextromethorphan (DM), [(+)-alpha-(4-chlorophenyl)-4- [(phenyl)methyl-1-piperidine ethanol] (SL 82.0715), (+)3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP), cis-4-phosphonomethyl-2-piperidine-carboxylic acid (CGS 19755) have been compared to those of PCP in rats. The rank of potency for inducing PCP-like EEG stages 1-3 was as follows: MK 801 > PCP > CGS 19755 > CPP. These drugs also induced PCP-like behavioural effects. On the contrary, DM and SL 82.0715, administered up to the dose of 100 mg/kg IP, failed to induce PCP-like behavioural effects and elicited only the stage 1 of PCP-like EEG. These results strongly suggest the involvement of NMDA neurotransmission in the behavioral and EEG effects of PCP.