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

Tangui Maurice, Tsung Ping Su, Daniel W. Parish, Toshitaka Nabeshima, Alain Privat

Research output: Contribution to journalArticle

93 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)859-869
Number of pages11
JournalPharmacology, Biochemistry and Behavior
Volume49
Issue number4
DOIs
Publication statusPublished - 12-1994

Fingerprint

Dizocilpine Maleate
Learning
Amnesia
Derivatives
Data storage equipment
Mecamylamine
Scopolamine Hydrobromide
Long-Term Memory
Haloperidol
N-Methylaspartate
N-Methyl-D-Aspartate Receptors
Short-Term Memory
Cognition
Cholinergic Agents
Modulation
2-(4-morpholino)ethyl-1-phenylcyclohexane-1-carboxylate
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Toxicology
  • Pharmacology
  • Clinical Biochemistry
  • Biological Psychiatry
  • Behavioral Neuroscience

Cite this

Maurice, Tangui ; Su, Tsung Ping ; Parish, Daniel W. ; Nabeshima, Toshitaka ; Privat, Alain. / PRE-084, a σ selective PCP derivative, attenuates MK-801-induced impairment of learning in mice. In: Pharmacology, Biochemistry and Behavior. 1994 ; Vol. 49, No. 4. pp. 859-869.
@article{c0cfc331828649f8a50f03f23a59317a,
title = "PRE-084, a σ selective PCP derivative, attenuates MK-801-induced impairment of learning in mice",
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.",
author = "Tangui Maurice and Su, {Tsung Ping} and Parish, {Daniel W.} and Toshitaka Nabeshima and Alain Privat",
year = "1994",
month = "12",
doi = "10.1016/0091-3057(94)90235-6",
language = "English",
volume = "49",
pages = "859--869",
journal = "Pharmacology Biochemistry and Behavior",
issn = "0091-3057",
publisher = "Elsevier Inc.",
number = "4",

}

PRE-084, a σ selective PCP derivative, attenuates MK-801-induced impairment of learning in mice. / Maurice, Tangui; Su, Tsung Ping; Parish, Daniel W.; Nabeshima, Toshitaka; Privat, Alain.

In: Pharmacology, Biochemistry and Behavior, Vol. 49, No. 4, 12.1994, p. 859-869.

Research output: Contribution to journalArticle

TY - JOUR

T1 - PRE-084, a σ selective PCP derivative, attenuates MK-801-induced impairment of learning in mice

AU - Maurice, Tangui

AU - Su, Tsung Ping

AU - Parish, Daniel W.

AU - Nabeshima, Toshitaka

AU - Privat, Alain

PY - 1994/12

Y1 - 1994/12

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0027944759&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0027944759&partnerID=8YFLogxK

U2 - 10.1016/0091-3057(94)90235-6

DO - 10.1016/0091-3057(94)90235-6

M3 - Article

C2 - 7886099

AN - SCOPUS:0027944759

VL - 49

SP - 859

EP - 869

JO - Pharmacology Biochemistry and Behavior

JF - Pharmacology Biochemistry and Behavior

SN - 0091-3057

IS - 4

ER -