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 language | English |
|---|---|
| Pages (from-to) | 859-869 |
| Number of pages | 11 |
| Journal | Pharmacology, Biochemistry and Behavior |
| Volume | 49 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 12-1994 |
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All Science Journal Classification (ASJC) codes
- Biochemistry
- Toxicology
- Pharmacology
- Clinical Biochemistry
- Biological Psychiatry
- Behavioral Neuroscience
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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 journal › Article
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 -