PRE-084, a σ selective PCP derivative, attenuates MK-801-induced impairment of learning in mice

doi:10.1016/0091-3057(94)90235-6

Pharmacology Biochemistry and Behavior

Volume 49, Issue 4, December 1994, Pages 859-869

https://doi.org/10.1016/0091-3057(94)90235-6 Get rights and content

Abstract

We investigated the effect of the σ selective PCP derivative PRE-084 on the impairment of learning induced in mice by the noncompetitive NMDA antagonist MK-801. Learning capacities were evaluated using the spontaneous alternation in a Y-maze test for spatial working memory, the step-down passive avoidance and the elevated plus-maze test for long-term memory. At doses about 1 mg/kg IP, PRE-084 significantly attenuated MK-801 (0.2 mg/kg IP) induced impairment of learning. The dose-response curve was bell-shaped which is typical for cognition enhancers. The effect of PRE-084 was antagonized by BMY-14802 (10 mg/kg IP) and suppressed by a chronic treatment with haloperidol (4 mg/kg/day SC for 7 days). Furthermore, PRE-084 did not affect scopolamine (1 mg/kg SC) induced amnesia but significantly attenuated mecamylamine (10 mg/kg IP) induced amnesia. These results show that σ sites mediate a modulation of the NMDA receptor complex-dependent learning processes and may similarly affect the cholinergic nicotinic memory processes. Moreover, the PCP derivative PRE-084, acting selectively at σ sites, reverses the amnesia induced by a drug acting at the PCP site.

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Moreover, neither the racemate of Norfenfluramine, nor the (+)- or (−)-isomer attenuated dizocilpine-induced deficits in the dose range tested (Fig. 1g–l). As previously described [37], the reference S1R agonist PRE-084 showed an anti-amnesic effect at 0.3 and 1 mg/kg in both tests (Fig. 2a and b). Both (+)- and (−)-Norfenfluramine prevented the anti-amnesic effects of PRE-084 (Fig. 2c and d), and therefore acted likely as S1R antagonists.
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PRE-084, a σ selective PCP derivative, attenuates MK-801-induced impairment of learning in mice

Abstract

Brain Res.

Eur. J. Pharmacol.

Eur. J. Pharmacol.

Neuropharmacology

Eur. J. Pharmacol.

Neurosci. Lett.

Neuropharmacology

Brain Res.

Brain Res.

Brain Res.

Eur. J. Pharmacol.

Trends Pharmacol. Sci.

Trends Pharmacol. Sci.

Eur. J. Pharmacol.

Eur. J. Pharmacol.

Brain Res.

The dissociative anesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N-methyl-D-aspartate

J. Pharmacol. Exp. Ther.

Apomorphine does not reverse reduced basal dopamine release in rat striatum and nucleus accumbens after chronic haloperidol treatment

Brain Res.

Utility of an elevated plus-maze for the evaluation of memory in mice: effect of nootropics, scopolamine and electroconvulsive shock

Psychopharmacology

Dynorphin A-(1–13) potently prevents memory dysfunctions induced by transient cerebral ischemia in mice

Eur. J. Pharmacol.

Differential regulation of σ and PCP receptors after chronic administration of haloperidol and phencyclidine in mice

FASEB J.

The dissociative anesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by $N- methyl- D -aspartate$