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
N1 - Funding Information:
Thanks are due to Jean Bayle for his dexterity in elaborating the apparatus used for behavioral testing; to Drs. Brian Lockhart and Jacques Vignon for their critical reading of the manuscript; to Pr. Tsutomu Kameyama and to Dr. Masayuki Hiramatsu for helpful discussions before initiating these experiments; and to Dr. Jean-Marc Kamenka for his generous gift of TCP and BTCP. This study was supported by the Institut de Recherche sur la Motile Epini6re and the Association Franqaise contre les Myopathies.
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.
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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 -