Metaphit fails to antagonize PCP-induced passive avoidance deficit

doi:10.1016/0091-3057(91)90618-C

Pharmacology Biochemistry and Behavior

Volume 38, Issue 1, January 1991, Pages 231-233

https://doi.org/10.1016/0091-3057(91)90618-C Get rights and content

Abstract

Pretreatment with metaphit (1-[1-(3-isothiocyanotophenyl)cyclohexyl]piperdine), a putative irreversible antagonist of phenycyclidine (PCP) receptors, did not antagonize PCP-induced passive avoidance deficit in rats, and did not decrease [³H]MK-801 (5-methyl-10,11-dihydro-5H-dibenzocyclohepten-5,10-imine maleate) binding to PCP recognition sites coupled to NMDA receptors. The effectiveness of the metaphit treatment was evidenced by the occurence of audiogenic seizures. These results suggest that previously reported antagonism in vivo actions of PCP by metaphit, is mediated by sites not involved in PCP-induced passive avoidance deficit, and not related to the NMDA receptor complex in brain structures studied (striatum, hippocampus, and cortex).

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The effects of NMDA (N -methyl- $d$ -aspartic acid) on metaphit (1-[1(3-isothiocyanatophenyl)-cyclohexyl]piperidine)-induced audiogenic seizures in adult male Wistar albino rats were studied with the aim of developing a suitable animal model of seizures. The animals were divided into four experimental groups: 1, saline control; 2, metaphit-injected; 3, metaphit + NMDA administered and 4, NMDA-treated. Upon the treatment, the rats were exposed to sound stimulation ( 100 ± 3 dB, for 60 s) at hourly intervals and the incidence and severity (running, clonus and tonus) of seizures were analysed. In group 3, only the animals which did not exhibit any metaphit-induced audiogenic seizures over 8 h were given a subconvulsive NMDA dose after the eigth audiogenic testing. For EEG recordings, three gold-plated screws were implanted into the rat skull. In most animals, metaphit led to EEG abnormalities and elicited epileptiform activity recorded as spikes, polyspikes and spike-wave complexes. Maximum incidence and severity of metaphit-induced convulsions occurred 8 h after injection (incidence 9/12), abating gradually until disappearing 30 h later. NMDA alone provoked no seizure response but the initial signs characterized by isolated spike activity evolving into sporadic slow-wave complexes, thus representing a proconvulsive brain state, were observed. This compound led to stereotyped behaviour seen as asymmetric posture, loss of righting reflex and tonic hind limb extension lasting for 60–90 min. It also potentiated metaphit-induced audiogenic seizures. Potentiation of metaphit-related audiogenic seizures by NMDA was recorded in three out of 17 rats that had never displayed seizures in eight previous testings, with a maximum incidence of eight out of 17 animals, 13–14 h after metaphit administration and seizures lasted for 10 h.
Effects Of ketamine, a noncompetitive NMDA antagonist, on the acquisition of the lever-press response in rats
1995, Physiology and Behavior
We analyzed the effects of ketamine, a noncompetitive NMDA antagonist, on the acquisition of the lever-press response in the Skinner box and on motor performance both in the open field and in the inclined screen. Ninety-six adult male Wistar rats were assigned at random to eight different groups (n = 12). The first four groups received an acute intraperitoneal (IP) injection of[ (a) physiological saline, (b) 4 mg/kg ketamine, (c) 8 mg/kg ketamine, or (d) 12 mg/kg ketamine, and the subjects were tested in a free lever-press response shaping in the Skinner box. The second four groups received the same substances and doses as the first four, but the subjects were tested for locomotor activity in an open field and tested immediately afterwards for motor performance in an 80 inclined screen. Results showed that ketamine impaired the acquisition of the lever-press response in a dose-dependent manner, with no effects on ambulation in the open field nor on length of stay in the inclined screen. These results suggest that ketamine effects on the acquisition of the lever-press response cannot be attributed to a motor impairment, indicating a possible specific effect of ketamine on the associative learning acquisition.

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Brief communicationMetaphit fails to antagonize PCP-induced passive avoidance deficit

Abstract

Neuropharmacology

Eur. J. Pharmacol.

Pharmacol. Biochem. Behav.

Eur. J. Pharmacol.

Life Sci.

Eur. J. Pharmacol.

Neurosci. Lett.

FEBS Lett.

Neuropharmacology

Life Sci.

The dissociative anesthetics ketamine and phencyclidine, selectively inhibit excitation of central mammalian neurons by N-methylaspartate

Br. J. Pharmacol.

Brief communication
Metaphit fails to antagonize PCP-induced passive avoidance deficit