Among the methods valuable for assessing spatial learning and memory impairments in rodents, the Barnes maze (BM) task deserves special attention. It is based on the assumption that the animal placed into the aversive environment should learn and remember the location of an escape box located below the surface of the platform. Different phases of the task allow to measure spatial learning, memory retrieval, and cognitive flexibility. Herein, we summarize current knowledge about the BM procedure, its variations and critical parameters measured in the task. We highlight confounding factors which should be taken into account when conducting BM task, discussing briefly its advantages and disadvantages. We then propose an extended version of the BM protocol which allows to measure different aspects of spatial learning and memory in rodents. We believe that this review will help to standardize the BM methodology across the laboratories and eventually make the results comparable.
Anxiety disorder is a great challenge for modern psychopharmacology. Although a variety of single drugs are used in the treatment of anxiety, it is important to search for new therapeutics with faster onset of action, fewer side effects, and higher efficacy. In this work, we studied the possible anxiolytic action mechanism of two new arylpiperazine derivatives: compounds 4p N‐(3‐(4‐(piperonyl)piperazin‐1‐yl)propyl)isonicotinamide and 3o N‐(2‐(4‐(pyrimidin‐2‐yl)piperazin‐1‐yl)ethyl)picolinamide, focusing on their effects on the GABAergic and 5‐HT systems. The elevated plus‐maze test (EPM) was used for measuring anxiety. Additionally, in order to elucidate whether the new compounds have impact on the central redox balance, we conducted biochemical studies. In doing so, the relative activity of the enzymes responsible for glutathione metabolism – glutathione peroxidase and reductase (GPx and GR) – was measured. The results of the presented studies confirmed the anxiolytic effects of the new compounds 4p (60 mg/kg) and 3o (7.5 mg/kg), and suggested in the mechanism of their action, direct 5‐HT1A receptors’ participation and indirect involvement of the GABAergic system. Furthermore, the compounds exerted significant agonistic effect with buspirone (BUS, the 5‐HT1A partial agonist, 1 mg/kg i.p.) and diazepam (DZ, the classic benzodiazepine anxiolytic, 0.25 mg/kg s.c.), while WAY 100635 (N‐{2‐[4‐(2‐methoxyphenyl)‐1‐piperazinyl] ethyl}‐N‐(2‐pyridyl) cyclohexanecarboxamide, a selective 5‐HT1A antagonist, 0.1 mg/kg s.c.), but not flumazenil (a GABAA‐BDZ receptor complex antagonist, 10 mg/kg i.p.) was able to reverse their anxiolytic effects in EPM. A concomitant decrease in GPx by the compound 4p (and to a lesser degree, by compound 3o) further seemed to confirm their anxiolytic and antioxidant activity.
How to get a new drug to market? How much time does it take to go from the idea to implementation? In this study we followed the path drugs take from synthesis to introduction to the market. In doing so, articles in the PubMed and the Google Scholar database have been analyzed using the keywords: drug development, drug design, lead compound, preclinical trials, clinical trials. The available literature was subjectively selected due to its usefulness in the topic. Based on the obtained articles, we presented the stages that a would-be drug takes on the way from the idea to marketing. Herein, it is underlined that the process of creating new drugs is long, extremely labor-intensive, and involves many restrictions in the context of the use of animals, as well as humans
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