Background
Accumulating evidence suggests that α7 nicotinic receptor (α7 nAChR) agonists could
be potential therapeutic drugs for cognitive deficits in schizophrenia. The present
study was undertaken to examine the effects of the novel selective α7 nAChR agonist
SSR180711 on cognitive deficits in mice after repeated administration of the N-methyl-D-aspartate
receptor antagonist phencyclidine (PCP).
Methods
Saline or PCP (10 mg/kg/day for 10 days) was administered to mice. Subsequently, vehicle,
SSR180711 (.3 or 3.0 mg/kg/day), SSR180711 (3.0 mg/kg/day) + the selective α7 nAChR
antagonist methyllycaconitine (MLA; 3.0 mg/kg/day), or MLA (3.0 mg/kg/day) was administered
IP for 2 consecutive weeks. Twenty-four hours after the final administration, a novel
object recognition test was performed.
Results
The PCP-induced cognitive deficits were significantly improved by subsequent subchronic
(2-week) administration of SSR180711 (3.0 mg/kg). The effects of SSR180711 (3.0 mg/kg)
were significantly antagonized by co-administration of MLA (3.0 mg/kg). Furthermore,
Western blot analysis and immunohistochemistry revealed that levels of α7 nAChRs in
the frontal cortex and hippocampus of the PCP (10 mg/kg/day for 10 days)-treated mice
were significantly lower than those of saline-treated mice.
Conclusions
These findings suggest that repeated PCP administration significantly decreased the
density of α7 nAChRs in the brain and that the α7 nAChR agonist SSR180711 could ameliorate
cognitive deficits in mice after repeated administration of PCP. Therefore, α7 nAChR
agonists including SSR180711 are potential therapeutic drugs for treating cognitive
deficits in schizophrenic patients.
Key Words
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Article info
Publication history
Published online: June 30, 2007
Accepted:
April 24,
2007
Received in revised form:
April 12,
2007
Received:
December 5,
2006
Identification
Copyright
© 2008 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
