Alterations in acetylcholine, NMDA, benzodiazepine receptors and protein kinase C in the brain of the senescence-accelerated mouse: an animal model useful for studies on cognitive enhancers.
The senescence-accelerated mouse (SAMP8) is a useful murine model of accelerated aging and learning deficiency. We examined bindings of [3H]pirenzepine, [3H]dizocilpine (MK-801), [3H]flunitrazepam, [3H]8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) and [3H]phorbol 12,13-dibutylate (PDBu) in SAMP8 brains, and compared them to those of SAMR1 (control). In the hippocampus of SAMP8 at 12 months, bindings of [3H]pirenzepine, [3H]MK-801, [3H]flunitrazepam, [3H]8-OH-DPAT and [3H]PDBu were significantly lower than those in SAMR1. In the cerebral cortex, bindings of [3H]pirenzepine, [3H]flunitrazepam and [3H]8-OH-DPAT were higher in SAMP8 than in SAMR1 at 12 months. [3H]PDBu binding was decreased in both the fractions of the membrane and cytosol in the hippocampus of SAMP8. The neurochemical findings presented here support behavioral and pharmacological findings that SAMP8 is a useful model of learning dysfunction and anxiety-deficiency. The usefulness of SAMP8 in studies on cognitive enhancers is also discussed.
Nomura
Y
Y
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
Kitamura
Y
Y
Ohnuki
T
T
Arima
T
T
Yamanaka
Y
Y
Sasaki
K
K
Oomura
Y
Y
D000375:Aging / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D001923:Brain Chemistry / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018697:Nootropic Agents / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism*; D011869:Radioligand Assay; D011950:Receptors, Cholinergic / Q000378:metabolism*; D011963:Receptors, GABA-A / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*
D018697:Nootropic Agents; D011950:Receptors, Cholinergic; D011963:Receptors, GABA-A; D011976:Receptors, Muscarinic; D016194:Receptors, N-Methyl-D-Aspartate; D011493:Protein Kinase C