title: Differences in results from in vivo and in vitro studies on the use-dependency of N-methylaspartate antagonism by MK-801 and other phencyclidine receptor ligands.
abstract: We have used microelectrophoretic and intravenous administration of drugs to rat spinal cord neurones in vivo and bath application to rat cortical wedges in vitro to evaluate MK-801 and other phencyclidine (PCP) receptor ligands as N-methylaspartate (NMA) antagonists, paying particular regard to the possible use-dependent nature of their action. MK-801, 0.1-0.5 mg/kg, was a selective and long-lasting NMA antagonist. We were unable to demonstrate significant use-dependent onset of antagonism of NMA by any of the drugs in vivo. Recovery, however, for MK-801 was use-dependent. In vitro there was a gradation with MK-801 being very use-dependent, followed by (PCP), cyclazocine and ketamine, the last showing little or no use-dependence. Results of experiments modulating the in vitro environment suggest that a significant difference between the in vitro and in vivo systems was temperature. Raising the temperature of the wedge chamber from 23 to 33 degrees C reduced the use-dependence of MK-801, and lowering the temperature to 13 degrees C increased the use-dependence of PCP. The mechanism of action of PCP receptor ligands is discussed in the light of these results.
authors.affiliation: Department of Physiology, Royal Veterinary College, London, U.K.
authors.forename: S N
authors.initials: SN
authors.lastname: Davies
authors.forename: D
authors.initials: D
authors.lastname: Martin
authors.forename: J D
authors.initials: JD
authors.lastname: Millar
authors.forename: J A
authors.initials: JA
authors.lastname: Aram
authors.forename: J
authors.initials: J
authors.lastname: Church
authors.forename: D
authors.initials: D
authors.lastname: Lodge
mesh_terms: D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors; D002540:Cerebral Cortex / Q000187:drug effects; D003986:Dibenzocycloheptenes / Q000494:pharmacology*; D016291:Dizocilpine Maleate; D066298:In Vitro Techniques; D007649:Ketamine / Q000494:pharmacology*; D016202:N-Methylaspartate; D010622:Phencyclidine / Q000494:pharmacology; D051381:Rats; D017981:Receptors, Neurotransmitter / Q000187:drug effects*; D017478:Receptors, Phencyclidine; D013116:Spinal Cord / Q000187:drug effects; D019966:Substance-Related Disorders
chemical_list: D003986:Dibenzocycloheptenes; D017981:Receptors, Neurotransmitter; D017478:Receptors, Phencyclidine; D001224:Aspartic Acid; D016202:N-Methylaspartate; D007649:Ketamine; D016291:Dizocilpine Maleate; D010622:Phencyclidine