Since its development about 40 years ago (1981–2021), Morris water maze has turned into a very popular tool for assessing spatial learning and memory. Its many advantages have ensured its pertinence to date. These include its effectiveness in evaluating hippocampal-dependent learning and memory, exemption from motivational differences across diverse experimental manipulations, reliability in various cross-species studies, and adaptability to many experimental conditions with various test protocols. Nonetheless, throughout its establishment, several experimental and analysis loopholes have galvanized researchers to assess ways in which it could be improved and adapted to fill this gap. Therefore, in this review, we briefly summarize these developments since the early years of its establishment through to the most recent advancements in computerized analysis, offering more comprehensive analysis paradigms. In addition, we discuss the adaptability of the Morris water maze across different test versions and analysis paradigms, providing suggestions with regard to the best paradigms for particular experimental conditions. Hence, the proper selection of the experimental protocols, analysis paradigms, and consideration of the assay’s limitations should be carefully considered. Given that appropriate measures are taken, with various adaptations made, the Morris water maze will likely remain a relevant tool to assess the mechanisms of spatial learning and memory.

The multidrug resistance phenomenon presents a major threat to the pharmaceutical industry. This resistance is a common occurrence in several diseases and is mediated by multidrug transporters that actively pump substances out of the cell and away from their target regions. The most well-known multidrug transporter is the P-glycoprotein transporter. The binding sites within P-glycoprotein can accommodate a variety of compounds with diverse structures. Hence, numerous drugs are P-glycoprotein substrates, with new ones being identified every day. For many years, the mechanisms of action of P-glycoprotein have been shrouded in mystery, and scientists have only recently been able to elucidate certain structural and functional aspects of this protein. Although P-glycoprotein is highly implicated in multidrug resistant diseases, this transporter also performs various physiological roles in the human body and is expressed in several tissues, including the brain, kidneys, liver, gastrointestinal tract, testis, and placenta. The expression levels of P-glycoprotein are regulated by different enzymes, inflammatory mediators and transcription factors; alterations in which can result in the generation of a disease phenotype. This review details the discovery, the recently proposed structure and the regulatory functions of P-glycoprotein, as well as the crucial role it plays in health and disease.

The pilocarpine animal model of status epilepticus is a well-established, clinically translatable model that satisfies all of the criteria essential for an animal model of status epilepticus: a latency period followed by spontaneous recurrent seizures, replication of behavioural, electrographic, metabolic, and neuropathological changes, as well as, pharmacoresistance to anti-epileptic drugs similar to that observed in human status epilepticus. However, this model is also characterized by high mortality rates and studies in recent years have also seen difficulties in seizure induction due to pilocarpine resistant animals. This can be attributed to differences in rodent strains, species, gender, and the presence of the multi-transporter, P-glycoprotein at the blood brain barrier. The current paper highlights the various alterations made to the original pilocarpine model over the years to combat both the high mortality and low induction rates. These range from the initial lithium-pilocarpine model to the more recent Reduced Intensity Status Epilepticus (RISE) model, which finally brought the mortality rates down to 1%. These modifications are essential to improve animal welfare and future experimental outcomes.

Cancer is one of the leading causes of death in both developed and developing countries. Due to its heterogenous nature, it occurs in various regions of the body and often goes undetected until later stages of disease progression. Feasible treatment options are limited because of the invasive nature of cancer and often result in detrimental side-effects and poor survival rates. Therefore, recent studies have attempted to identify aberrant expression levels of previously undiscovered proteins in cancer, with the hope of developing better diagnostic tools and pharmaceutical options. One class of such targets is the π-subunit-containing γ-aminobutyric acid type A receptors. Although these receptors were discovered more than 20 years ago, there is limited information available. They possess atypical functional properties and are expressed in several non-neuronal tissues. Prior studies have highlighted the role of these receptors in the female reproductive system. New research focusing on the higher expression levels of these receptors in ovarian, breast, gastric, cervical, and pancreatic cancers, their physiological function in healthy individuals, and their pro-tumorigenic effects in these cancer types is reviewed here.