Chronic treatments with tacrine and (-)-nicotine induce different changes of nicotinic and muscarinic acetylcholine receptors in the brain of aged rat.
The present study evaluated effects of chronic treatment with tacrine and (-)-nicotine for 21 days on nicotinic and muscarinic acetylcholine receptors in the brains of old rats (24-25 months) by receptor autoradiography. The nicotinic receptor (nAChR) binding sites were measured by (-)-[3H]nicotine and [3H]epibatidine, and the muscarinic receptor (mAChR) binding sites by [3H]pirenzepine and [3H]AFDX 384. No change in (-)-[3H]nicotine binding was observed in all of the brain regions analysed following chroinic treatment with tacrine (10 mg/kg). Similarly, the [3H]epibatidine binding was not changed in most of the brain regions analysed except for a few brain regions where a decrease was observed in tacrine treated animals compared to control animals. Chronic treatment with (-)-nicotine (0.45 mg base/kg) significantly increased both (-)-[3H]nicotine and [3H]epibatidine bindings in every brain regions analysed except for the hippocampus when measured by (-)-[3H]nicotine. A significant decrease in [3H]AFDX 384 binding, but not in [3H]pirenzepine binding was observed in all of the brain regions analysed following the treatment with tacrine. These data suggest that chronic treatments with tacrine and (-)-nicotine differentially interfere and regulate the subtypes of nAChRs and mAChRs in the brain of aged rat. These data differ from what have been earlier observed in the brain of young adult rat following tacrine treatment, revealing some dynamic changes in receptor properties in the brain during aging.
Zhang
X
X
Division of Molecular Neuropharmacology, Department of Clinical Neuroscience, Occupational Therapy and Elderly Care Research (NEUROTEC), Karolinska Institutet, Huddinge University Hospital, Huddinge, Sweden. xiao.zhang@neurotec.ki.se
Tian
J-Y
JY
Svensson
A-L
AL
Gong
Z-H
ZH
Meyerson
B
B
Nordberg
A
A
D000375:Aging / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D001665:Binding Sites / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D004334:Drug Administration Schedule; D008297:Male; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D010277:Parasympathomimetics / Q000494:pharmacology*; D010890:Pirenzepine / Q000031:analogs & derivatives*; D011725:Pyridines / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D011976:Receptors, Muscarinic / Q000187:drug effects* / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000378:metabolism; D013619:Tacrine / Q000494:pharmacology*; D014316:Tritium
D019086:Bridged Bicyclo Compounds, Heterocyclic; D018722:Nicotinic Agonists; D010277:Parasympathomimetics; D011725:Pyridines; D011976:Receptors, Muscarinic; D011978:Receptors, Nicotinic; D014316:Tritium; C065959:AFDX 384; D010890:Pirenzepine; D013619:Tacrine; D009538:Nicotine; C082748:epibatidine