Research Article - (2020) Volume 8, Issue 6
Received: 25-Sep-2020
Published:
12-Oct-2020
Citation: Majidi, Mohammad Reza. “Effects of Fluoxetine on Memory Processes in the Rats with Different Phenotypes of Nervous System and Different Levels of Biogenic Monoamines of the Brain.” J Neurol Disord 8 (2020): 436. doi: 10.37421/jnd.2020.8.436.
Copyright: © 2020 Majidi MR. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
The present paper explores the effects of the psychopharmacological agent - fluoxetine - on mnestic processes, using a model of passive avoidance on male Wistar rats with different nervous system phenotypes and different activity ratios of the monoaminergic systems of the brains. In the re-test session under administration of fluoxetine, the seizure-tolerant rats compared to the seizure-sensitive rats were characterized by a more pronounced fear response to the "unsafe" compartment and enhanced anxiety facilitating the retention of memory trace. The individual sensitivity of the animals to the action of fluoxetine and the direction of its effects on mnestic processes are supposed to be determined by different primary activity ratios of the monoaminergic systems of the brain.
Seizure-tolerant and seizure-sensitive rats • Passive avoidance response • Fluoxetine • Serotonin • Dopamine• Noradrenaline
In recent years, increasing attention has been paid to the study of the functional specificity of the central nervous system (CNS), determined by both genetic (different strains of rats) and individual (differences within one strain) peculiarities of behaviour, memory, learning, adaptation and plasticity. It is known, that the individual reactivity of organism to the action of different stress-factors are associated with the innate difference in activities of the monoaminergic (MA) systems of the brain, involved in the neurochemical organization of various types of innate and learned behaviour [1]. In this regard, the most significant neurotransmitter is serotonin (5-HT) being an important biochemical factor forming mixed anxiety-depressive disorders and disturbing cognitive functions [2]. In particular, deficiency of 5-HT leads to a disturbance of synaptic transmission in the CNS and forms depressive states. Therefore, most psychotropic medications applied in medical practice are targeted at enhancing serotonin neurotransmission. Among the medications that affect intra-synaptic serotonin metabolism, the selective serotonin reuptake inhibitors, such as fluoxetine, play a key role [3]. The medication binds to the specific protein – serotonin transporter – selectively blocking serotonin reuptake in the presynaptic ending, which leads to increase in concentration of the neurotransmitter in the synaptic cleft and to enhancing its action on the postsynaptic receptors.
A lot of scientific papers are dedicated to the comparative study of the effects of acute and chronic administration of fluoxetine on behaviour in various models of rats and mice of different strains [4,5]. In addition, they contain the information about the variety of the neuro-psychotropic medications that depends on the animal genotype, nature of the test conditions [6] and the baseline psycho-emotional state of the individuals [7].
Based on the aforementioned, of particular interest is to study the effects of 5-HT excess caused by fluoxetine on the mnestic processes, using a model of passive avoidance (PA) on male Wistar rats with different nervous system phenotypes and different activity ratios of the catecholaminergic and 5-HT-ergic systems of the brain. Passive avoidance test is one of the main techniques of testing neuro-psychotropic medications' effects and, moreover, it is especially popular in studying mnestic process patterns [8].
The study was carried out on male Wistar rats (body mass of 180-220 g) under chronic conditions. The rats were preliminarily tested for tolerance to acoustic startle stimulus. For that purpose, each animal was exposed to the sound of an electric bell (90-120 dB) for 2 min in the soundproof box. The indicator of sensitivity was the intensity of seizure in the rats. The difference in the responses to acoustic stimulus allowed dividing the animals into 2 groups: seizure-sensitive (SS – prone to seizures) and seizure-tolerant (ST – without motor excitation) rats.
From the total number (121) of the rats, 29 ST and 27 SS rats were selected. Both types of the animals were divided into the experimental and control animals. 1 h prior to the experiment, the experimental animals (ST (n=15), SS (n=14)) were intraperitoneally injected with fluoxetine (Pharm science, Montreal, Canada) at a dose of 25mg/kg. The control rats (ST (n=14), SS (n=13)) were administered with the diluent - distilled water - in the equal volume. During 2 days prior to the main experiments, the animals were handled for 5 min per day in order to equalize their responses to this stimulus.
PA-elaboration was carried out according to the common technique in the light-dark box. The rats were placed in the light compartment with their tails to the guillotine door between the light and dark compartments. The latency to enter the dark compartment was recorded (unconditioned "mink" reflex). When the animal entered the dark compartment, the guillotine door was closed and a mild electric foot shock (0.5 mA; 2 sec) was delivered through the grid floor. Then the animals were quickly removed. The stability of the formed response was characterized by the degree of its retention in the re-test session on the 2nd day, which allowed identifying the peculiarities of the memory traces retention. The time spent by the animals in the light "safe" compartment was recorded for 300 sec. The behavioural (search movements, rearing, grooming) and vegetative (number of faecal boluses) indices registered in PA re-test session were also analysed.
While processing the experimental material, we have considered the total time spent by the rats in the light compartment and the number of rats that retained the formed PA response, as well as analysed the range of behavioural (search movements, rearing, grooming) and vegetative (number of faecal boluses) indices in PA re-test session.
All the experimental procedures were carried out in accordance with the international and national standards for the care and use of laboratory animals and approved by the appropriate commit-tee of the Institute of Physiology, ANAS. The results of the study were processed with application of a nonparametric Mann–Whitney U test and Student's t-test. Mathematical calculations were performed using an analytics software package – STATISTICA.
Thus, extinction of mnestic processes, observed in our studies, under the effects of the medication in the SS rats is probably associated with weakening genetically determined activity of the 5-HT-ergic system of the hypothalamic while a better retention of memory traces in the ST rats is correlated with increased 5-HT- ergic and decreased NA-ergic systems' activity of the frontal cortex. The individual sensitivity of the animals to the action of the psychopharmacological agent – fluoxetine – and the direction of its effects on mnestic processes are supposed to be determined by different primary activity ratios of the MA-ergic systems of the brain.
I would like to express my deep gratitude to Prof. Ulduz Hashimova, Director of the Institute of Physiology, ANAS for enabling me to perform my experiments at the Institute and to Dr. Khadija Ismayilova, my research supervisor, for planning and development of this research work. My special thanks are extended to Farhad Rustamov who translated the paper into English.
The author claims that there is no conflict of interests.
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