ACTIVATION OF THE DORSAL HIPPOCAMPAL NICOTINIC ACETYLCHOLINE RECEPTORS IMPROVES TAMOXIFEN-INDUCED MEMORY RETRIEVAL IMPAIRMENT IN ADULT FEMALE RATS

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 womenwhoreceive adjuvant chemotherapy for breast cancer is a common health problem, using female animal models for investigating the cognitive effects ofTAMadministration 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 (2-6 mg/kg) impaired memory retrieval. Pre-test intra-CA1 microinjection of nicotine (0.3-0.5 mu g/rat) reversed TAMinduced memory impairment. Pre-test intra-CA1 microinjection of mecamylamine (0.1-0.3 lg/rat) plus 2 mg/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 (6 mg/kg) producedmemoryimpairment but pre-test intra-CA1 microinjection of nicotine (0.5 lg/rat) had no effect on TAM response. Moreover, the administration of an ineffective dose of TAM (2 mg/kg) had no effect on memory retrieval in OVX rats, while pre-test intra-CA1 microinjection of mecamylamine (0.3 mu g/rat) impaired memory retrieval. Taken together, it can be concluded that the impairing effect of TAMon 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. (C) 2016 IBRO. Published by Elsevier Ltd. All rights reserved.