title: Activation of the dorsal hippocampal nicotinic acetylcholine receptors improves tamoxifen-induced memory retrieval impairment in adult female rats.
abstract: Tamoxifen (TAM), a selective estrogen receptor modulator, has frequently been used in the treatment of breast cancer. In view of the fact that cognitive deficits in women who receive adjuvant chemotherapy for breast cancer is a common health problem, using female animal models for investigating the cognitive effects of TAM administration may improve our knowledge of TAM therapy. Therefore, the present study assessed the role of dorsal hippocampal cholinergic nicotinic receptors (nAChRs) in the effect of TAM administration on memory retrieval in ovariectomized (OVX) and non-OVX female rats using a passive avoidance learning task. Our results showed that pre-test administration of TAM (2-6mg/kg) impaired memory retrieval. Pre-test intra-CA1 microinjection of nicotine (0.3-0.5μg/rat) reversed TAM-induced memory impairment. Pre-test intra-CA1 microinjection of mecamylamine (0.1-0.3μg/rat) plus 2mg/kg (an ineffective dose) of TAM impaired memory retrieval. Pre-test intra-CA1 microinjection of the same doses of nicotine and mecamylamine by themselves had no effect on memory retrieval. In OVX rats, the administration of TAM (6mg/kg) produced memory impairment but pre-test intra-CA1 microinjection of nicotine (0.5μg/rat) had no effect on TAM response. Moreover, the administration of an ineffective dose of TAM (2mg/kg) had no effect on memory retrieval in OVX rats, while pre-test intra-CA1 microinjection of mecamylamine (0.3μg/rat) impaired memory retrieval. Taken together, it can be concluded that the impairing effect of TAM on memory formation may be modulated by nAChRs of the CA1 regions. It seems that memory impairment may be considered as an important side effect of TAM.
authors.affiliation: Department of Animal Biology, School of Biology and Center of Excellence in Phylogeny of Living Organisms, College of Science, University of Tehran, Tehran, Iran.
authors.forename: Azam
authors.initials: A
authors.lastname: Tajik
authors.affiliation: Department of Animal Biology, School of Biology and Center of Excellence in Phylogeny of Living Organisms, College of Science, University of Tehran, Tehran, Iran; School of Cognitive Sciences, Institute for Research in Fundamental Sciences (IPM), Tehran, Iran. Electronic address: rezayof@khayam.ut.ac.ir.
authors.forename: Ameneh
authors.initials: A
authors.lastname: Rezayof
authors.affiliation: Department of Animal Biology, School of Biology and Center of Excellence in Phylogeny of Living Organisms, College of Science, University of Tehran, Tehran, Iran.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Ghasemzadeh
authors.affiliation: Department of Animal Biology, School of Biology and Center of Excellence in Phylogeny of Living Organisms, College of Science, University of Tehran, Tehran, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Sardari
mesh_terms: D000375:Aging; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects* / Q000502:physiology; D005260:Female; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008464:Mecamylamine / Q000494:pharmacology; D008568:Memory / Q000187:drug effects* / Q000502:physiology; D008569:Memory Disorders / Q000139:chemically induced / Q000188:drug therapy*; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D017208:Rats, Wistar; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000378:metabolism*; D013629:Tamoxifen / Q000494:pharmacology
chemical_list: D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic; D013629:Tamoxifen; D008464:Mecamylamine; D009538:Nicotine
keywords: dorsal hippocampus; female rat(s); mecamylamine; nicotine; passive avoidance learning; tamoxifen