We previously reported that (-)-nicotine and κ-opioid receptor gonists lessened impairment of learning and/or memory in several animal models. Furthermore, these drugs prevented neurodegenerative damage induced by ischemia or β-amyloid peptide (25-35). In the present study, we tested whether (-)-nicotine and U-50,488H prevent delayed-memory impairment induced by β-amyloid peptide (25-35), and changes of expression of α7-type nicotinic acetylcholine receptor mRNA and prodynorphin mRNA. Seven days after treatment with β-amyloid peptide (25-35) (9 nmol/mouse, i.c.v.), memory impairment was observed in the Y-maze test. Memory impairment was prevented when (-)-nicotine (6.16 μmol/kg, s.c.) or U-50,488H (21 μmol/kg, s.c.) was administered 1 h before, but not 1 h after, β-amyloid peptide (25-35) treatment. There was no change in prodynorphin mRNA or α7-type nicotinic acetylcholine receptor mRNA expression in the hippocampus 10 days after β-amyloid peptide (25-35) treatment alone. Of interest, mRNA expression of not only prodynorphin, but also the α7-type nicotinic acetylcholine receptor, was significantly decreased when U-50,488H was administered 1 h before, but not 1 h after, treatment with β-amyloid peptide (25-35). However, these changes were not observed after the administration of (-)-nicetine. These results suggest that activation of the κ-opioid system, but not α7-type nicotinic receptors has a neuroprotective effect on β-amyloid peptide (25-35)-induced memory impairment, and may be involved in the long-lasting changes in the expression of these mRNAs.
All Science Journal Classification (ASJC) codes
- Biochemistry, Genetics and Molecular Biology(all)
- History and Philosophy of Science