TY - JOUR
T1 - WAY 100635, a 5-HT(1A) receptor antagonist, prevents the impairment of spatial learning caused by intrahippocampal administration of scopolamine or 7-chloro-kynurenic acid
AU - Carli, Mirjana
AU - Bonalumi, Pierenrico
AU - Samanin, Rosario
PY - 1997/11/7
Y1 - 1997/11/7
N2 - The effect of WAY 100635, a 5-HT(1A) receptor antagonist, on the impairment of spatial learning caused by intrahippocampal administration of scopolamine, a cholinergic muscarinic receptor antagonist, or 7-chloro- kynurenic acid, an antagonist at the glycine site associated with the NMDA receptor complex, was studied in a two-platform spatial discrimination task. Scopolamine (4 μg/μl) or 7-chloro-kynurenic acid (3 μg/μl), administered bilaterally into the CA1 region of the dorsal hippocampus 10 min before each training session, impaired choice accuracy with no effect on choice latency and errors of omission. Administered subcutaneously at 1 (but not at 0.3) mg/kg 30 min before each training session, WAY 100635 did not modify the acquisition of spatial learning, but prevented the impairment of choice accuracy caused by intrahippocampal scopolamine or 7-chloro-kynurenic acid. These findings suggest that blockade of 5-HT(1A) receptors can compensate the loss of cholinergic or NMDA-mediated excitatory input to pyramidal cells in the hippocampus. The mechanisms involved and the importance of these findings for the symptomatic treatment of memory disorders in man are discussed.
AB - The effect of WAY 100635, a 5-HT(1A) receptor antagonist, on the impairment of spatial learning caused by intrahippocampal administration of scopolamine, a cholinergic muscarinic receptor antagonist, or 7-chloro- kynurenic acid, an antagonist at the glycine site associated with the NMDA receptor complex, was studied in a two-platform spatial discrimination task. Scopolamine (4 μg/μl) or 7-chloro-kynurenic acid (3 μg/μl), administered bilaterally into the CA1 region of the dorsal hippocampus 10 min before each training session, impaired choice accuracy with no effect on choice latency and errors of omission. Administered subcutaneously at 1 (but not at 0.3) mg/kg 30 min before each training session, WAY 100635 did not modify the acquisition of spatial learning, but prevented the impairment of choice accuracy caused by intrahippocampal scopolamine or 7-chloro-kynurenic acid. These findings suggest that blockade of 5-HT(1A) receptors can compensate the loss of cholinergic or NMDA-mediated excitatory input to pyramidal cells in the hippocampus. The mechanisms involved and the importance of these findings for the symptomatic treatment of memory disorders in man are discussed.
KW - 7-Chloro-kynurenic acid
KW - Glycine site
KW - Hippocampus
KW - NMDA receptor
KW - Rat
KW - Scopolamine
KW - Serotonin 5-HT(1A) receptor
KW - Spatial learning
KW - WAY 100635
UR - http://www.scopus.com/inward/record.url?scp=0031558630&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0031558630&partnerID=8YFLogxK
U2 - 10.1016/S0006-8993(97)81700-3
DO - 10.1016/S0006-8993(97)81700-3
M3 - Article
C2 - 9452205
AN - SCOPUS:0031558630
VL - 774
SP - 167
EP - 174
JO - Brain Research
JF - Brain Research
SN - 0006-8993
IS - 1-2
ER -