The Effect of A Modified Fragment of Neuropeptide Y on Spatial Memory and Learning in the Morris Water Maze

Neuropeptide Y (NPY) is a biologically active neuropeptide that is responsible for a large list of physiological processes. We propose a short modified fragment of NPY that should at least partially have a spectrum of biological activity of the original peptide. The compound was named nonapeptide NP9. The aim of our study was to investigate the ability of the modified fragment of NPY to influence spatial memory and learning. Materials and methods: the study was performed on 24 one-year-old random-bred female rats weight 220–250 g. The animals were divided into 3 groups of 8 rats each: treated with a solvent (0.9 % NaCl), a solution of peptide NP9 0.02 mg/kg and the drug “Semax” 0.1 mg/kg. All drugs were administered intranasally. The study of the effect of the peptide NP9 on spatial memory and learning ability was performed in the psychopharmacological test the Morris water maze. Navigation parameters were analyzed using Noldus EthoVision XT 14 video tracking software. The escape latency, the distance moved, the average velocity and the meander were recorded. An inter-quadrant analysis of rat behavior was also performed, for which the frequency of appearance and time spent in certain quadrants were recorded. Results: nonapeptide NP9 in the Morris water maze test demonstrated the ability to accelerate the time to find a hidden platform, reduce the distance traveled, meander, and optimize the search strategy. Conclusions: NP9 peptide has demonstrated the ability to positively influence learning and spatial memory. The improvement in cognitive performance of animals administered with the peptide NP9 was no less than that of the reference nootropic drug Semax. These results substantiate the feasibility of further research with the aim of pharmaceutical development of a new nootropic dru

Low-dose Digoxin Enhances the Anticonvulsive Potential of Carbamazepine and Lamotrigine in Chemo-induced Seizures with Different Neurochemical Mechanisms

"Non-antiepileptic" drugs have a strong potential as adjuvants in multidrug-resistant epilepsy treatment. In previous study the influence of low doses of digoxin, which do not affect the myocardium, on the anticonvulsant potential of classical commonly used anti-epileptic drugs under conditions of seizures, induced by pentylenetetrazole and maximal electroshock, has been investigated. The aim of the study was to investigate the influence of digoxin at a sub-cardiotonic dose on the anticonvulsant potential of carbamazepine and lamotrigine in experimental seizures with different neurochemical mechanisms. Material and methods: A total of 192 random-bred male albino mice weighting 22–25 g were used. Carbamazepine and lamotrigine were administered intragastrically in conditionally effective (ED50) and sub-effective (½ ED50) doses: carbamazepine at doses of 100 and 50 mg/kg; lamotrigine at doses of 25 and 12.5 mg/kg. Digoxin was administered subcutaneously at a sub-cardiotonic dose of 0.8 mg/kg as an adjuvant to carbamazepine and lamotrigine in ½ ED50. Picrotoxin (2.5 mg/kg subcutaneously); thiosemicarbazide (25 mg/kg intraperitoneally); strychnine (1.2 mg/kg subcutaneously); camphor (1000 mg/kg intraperitoneally) were used as convulsant agents. Results: It was found that digoxin not only has its own permanent anticonvulsant effect on different models of paroxysms with different neurochemical mechanisms of development, but also significantly enhances the anticonvulsant potential of carbamazepine (to a lesser extent – lamotrigine) regardless of the pathogenesis of experimental paroxysms. Conclusion: Based on the results, it can be concluded that digoxin has a high potential as an adjuvant medicine in complex epilepsy treatment because it enhances the efficiency of low-dose traditional anticonvulsants carbamazepine and lamotrigin