TY - JOUR
T1 - Chronic cerebral hypoperfusion disrupts discriminative behavior in acquired-learning rats
AU - Tanaka, Ken Ichi
AU - Wada, Naoko
AU - Hori, Koji
AU - Asanuma, Masato
AU - Nomura, Masahiko
AU - Ogawa, Norio
N1 - Funding Information:
This work was supported in part by a grant-in-aid for the Encouragement of Young Scientists from the Japanese Ministry of Education, Science, Sports and Culture. The authors thank Dr M. Gónez-Vargas and Ms S.N. Asanuma for their support with mACh-R binding assay. The authors also thank Mr O. Gon for his technical assistance.
PY - 1998/10/1
Y1 - 1998/10/1
N2 - We describe an 'acquired-learning' rat model that was used to investigate the effects of chronic cerebral hypoperfusion on the maintenance of previously acquired discriminative behavior using the discriminating learning task. Male Wistar rats, aged 11 weeks, were trained to discriminate between lamp-on and lamp-off states under an operant-type learning procedure. After 30 sessions, we selected 'acquired-learning' rats with an average discrimination ratio higher than 75% recorded during the last three sessions. Chronic hypoperfusion was then induced by permanent ligation of both common carotid arteries under pentobarbital anesthesia. The rats were tested after surgery over a period of 12 weeks and brain tissue was analyzed for muscarinic acetylcholine receptor (roACh-R) binding. Cerebral hypoperfusion resulted in a significant reduction in the discrimination ratio throughout the observation period, compared with sham-operated rats. However, chronic hypoperfusion would not affect on motor function. The maximum number of mACh- R examined 12 weeks after the operation was significantly reduced in the frontal cortex and hippocampus in the hypoperfusion group. Impaired discrimination learning was associated with a reduction in mACh-R. Our findings suggest that chronic cerebral hypoperfusion in acquired-learning rats is a useful model for investigating the pathophysiology of dementia and that cortical and/or hippocampal cholinergic systems contributes to learning impairment, at least, in our learning task.
AB - We describe an 'acquired-learning' rat model that was used to investigate the effects of chronic cerebral hypoperfusion on the maintenance of previously acquired discriminative behavior using the discriminating learning task. Male Wistar rats, aged 11 weeks, were trained to discriminate between lamp-on and lamp-off states under an operant-type learning procedure. After 30 sessions, we selected 'acquired-learning' rats with an average discrimination ratio higher than 75% recorded during the last three sessions. Chronic hypoperfusion was then induced by permanent ligation of both common carotid arteries under pentobarbital anesthesia. The rats were tested after surgery over a period of 12 weeks and brain tissue was analyzed for muscarinic acetylcholine receptor (roACh-R) binding. Cerebral hypoperfusion resulted in a significant reduction in the discrimination ratio throughout the observation period, compared with sham-operated rats. However, chronic hypoperfusion would not affect on motor function. The maximum number of mACh- R examined 12 weeks after the operation was significantly reduced in the frontal cortex and hippocampus in the hypoperfusion group. Impaired discrimination learning was associated with a reduction in mACh-R. Our findings suggest that chronic cerebral hypoperfusion in acquired-learning rats is a useful model for investigating the pathophysiology of dementia and that cortical and/or hippocampal cholinergic systems contributes to learning impairment, at least, in our learning task.
KW - Acquired- learning rats
KW - Chronic hypoperfusion
KW - Dementia
KW - Discrimination learning
KW - Muscarinic acetylcholine receptor
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U2 - 10.1016/S0165-0270(98)00092-2
DO - 10.1016/S0165-0270(98)00092-2
M3 - Article
C2 - 9821635
AN - SCOPUS:0032190944
VL - 84
SP - 63
EP - 68
JO - Journal of Neuroscience Methods
JF - Journal of Neuroscience Methods
SN - 0165-0270
IS - 1-2
ER -