en Pharmacokinetics/Dynamics Pharmacokinetics/Dynamics Experimental research article Experimental research article <p style="text-align: justify"><span style="font-size: 11px">Introduction: <font face="Arial,Arial"><font face="Arial,Arial">Although the initial hypothesis for the action of doxepin was based on the inhibition of the reuptake of neurotransmitters, it has been suggested that it may also involve other mechanisms. Therefore, this study aims to investigate the effect of doxepin on spatial memory, tumor necrosis factor alpha (TNF-&alpha) level, expression of pro-apoptotic </font></font>(Bad and Bax) and anti-<font face="Arial,Arial"><font face="Arial,Arial">apoptotic </font></font>(Bcl<font face="Arial,Arial"><font face="Arial,Arial">-2) genes in the rat hippocampus. </font></font></span><span style="font-size: 11px">Materials and Methods: <font face="Arial,Arial"><font face="Arial,Arial">Male rats were divided randomly into three groups the control, the doxepin 1 and 5 mg/kg, respectively). Rats received i.p injection of doxepin for 21 days. Spatial memory was evaluated by Morris water maze test. Then the hippocampi were dissected for measurement of the expression of Bcl2, Bad and Bax genes and the TNF-&alpha level. </font></font></span><span style="font-size: 11px">Results: <font face="Arial,Arial"><font face="Arial,Arial">Our results showed no significant effects of doxepin on spatial memory. Doxepin significantly decreased expression of Bad gene, but had no significant/considerable effects on Bcl2 and Bax gene expression. Also, the ratio of TNF-&alpha to total protein (%) did not show significant differences in the rat hippocampus. </font></font></span><span style="font-size: 11px">Conclusion: <font face="Arial,Arial"><font face="Arial,Arial">These results did not show any significant impact of doxepin on the factors affecting the neuronal functions in intact animals. However, Since a significant reduction in the hippocampal Bad mRNA levels was observed It is our assumption that doxepin has neuroprotective effects.</font></font></span></p> Doxepin, Memory, Hippocampus, Bcl-2 family, TNF-α. 185 192 http://ppj.phypha.ir/browse.php?a_code=A-10-886-1&slc_lang=en&sid=1 Nastaran Eidelkhani na.eidelkhani@yahoo.com 3200319475328460015622 3200319475328460015622 No Department of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran Maryam Radahmadi m_radahmadi@med.mui.ac.ir 3200319475328460015623 3200319475328460015623 No Department of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran Laleh Rafiee rafiee.laleh@gmail.com 3200319475328460015624 3200319475328460015624 No Applied Physiology Research Center, Isfahan University of Medical Sciences, Isfahan, Iran Mahsa Gharzi mahsagharzi@gmail.com 3200319475328460015625 3200319475328460015625 No Department of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran Hojjatallah Alaei alaei@med.mui.ac.ir 3200319475328460015626 3200319475328460015626 No Department of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran Parham Reisi p_reisi@med.mui.ac.ir 3200319475328460015627 3200319475328460015627 Yes Department of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran