Ameliorating effect offluoxetine on tamoxifen-induced memory loss: The role of corticolimbic NMDA receptors and CREB/BDNF/cFos signaling pathways in rats.

Tamoxifen-induced cognitive dysfunction may lead to fluoxetine consumption in patients with breast cancer. Since the brain mechanisms are unclear in tamoxifen/fluoxetine therapy, the blockade effect of hippocampal/amygdala/prefrontal cortical NMDA receptors was examined in fluoxetine/tamoxifen-induced memory retrieval. We also assessed the corticolimbic signaling pathways in memory retrieval under the drug treatment in adult male Wistar rats. Using the Western blot technique, the expression levels of the cAMP response element-binding protein (CREB), brain-derived neurotrophic factor (BDNF), and cFos were evaluated in the corticolimbic regions. The results showed that pre-test administration of fluoxetine (3 and 5 mg/kg, i.p.) improved tamoxifen-induced memory impairment in the passive avoidance learning task. Pre-test bilateral microinjection of D-AP5, a selective NMDA receptor antagonist, into the dorsal hippocampal CA1 regions and the central amygdala (CeA), but not the medial prefrontal cortex (mPFC), inhibited the improving effect of fluoxetine on tamoxifen response. It is important to note that the microinjection of D-AP5 into the different sites by itself did not affect memory retrieval. Memory retrieval increased the signaling pathway of pCREB/CREB/BDNF/cFos in the corticolimbic regions. Tamoxifen-induced memory impairment decreased the hippocampal/PFC BDNF level and the amygdala level of pCREB/CREB/cFos. The improving effect of fluoxetine on tamoxifen significantly increased the hippocampal/PFC expression levels of BDNF, the PFC/amygdala expression levels of cFos, and the ratio of pCREB/CREB in all targeted areas. Thus, NMDA receptors' activity in the different corticolimbic regions mediates fluoxetine/tamoxifen memory retrieval. The corticolimbic synaptic plasticity changes likely accompany the improving effect of fluoxetine on tamoxifen response.

The myth of when and where: How false assumptions still haunt theories of consciousness.

Recent advances in neural sciences have uncovered countless facts about the brain. Although there is a plethora of theories of consciousness, it seems to some philosophers that there is still an explanatory gap when it comes to a scientific account of subjective experience. In what follows, I argue why some of our more commonly acknowledged theories do not at all provide us with an account of subjective experience as they are built on false assumptions. These assumptions have led us into a state of cognitive dissonance between maintaining our standard scientific practices on the one hand, and maintaining our folk notions on the other. I end by proposing Illusionism as the only option for a scientific investigation of consciousness and that even if ideas like panpsychism turn out to be holding the seemingly missing piece of the puzzle, the path to them must go through Illusionism.