Hypothalamic melanortin receptor (MCR) activation inhibits appetite. Neuropeptide Y (NPY) and Agouti Related Protein (AgRP) are coexpressed in some hypothalamic neurons and stimulate feeding, NPY via inhibition of MCR-expressing neurons, and AgRP via MCR4 antagonism. Mutation yellow at the mouse agouti locus (Ау) evokes MCR blockage and stimulates appetite in nulliparous females. The role of MCRs in food intake regulation during pregnancy and lactation is unclear. In this study we measured hypothalamic AgRP and NPY mRNA levels in virgin and mated C57Bl a/a (control) and Ау/a females on days 7, 13, 18 of pregnancy, 10, 21 of lactation, and after offspring separation, AgRP immunoreactivity in virgin and lactating females, and correlated gene expression with food intake (FI). Virgin Ау/a compared to a/a 
females had higher FI and lower AgRP expression. Pregnant Ау/a and a/a mice showed different patterns of food intake and neuropeptide expressions. NPY mRNA levels increased during pregnancy only in a/a mice, while AgRP mRNA levels increased in both genotypes being lower in Ау/a then in a/a mice. In lactating Ау/a and a/a mice, AgRP expression and NPY mRNA level were similar. AgRP expression was higher in lactating then in virgin Ау/a mice. The results obtained demonstrate that in nonbreeding female mice, MCR blockage is associated with AgRP expression inhibition which vanishes in lactation. In lactation, hyperphagia is independent of MCR blockage. In pregnancy, food intake regulation involves MCR signaling and activation of NPY and AgRP expression.

It is known that neonatal handling may cause longterm changes in neurobiological and behavioral phenotypes. Neonatal handling of rats selected for enhanced aggressiveness towards humans (“aggressive” rats of generation 44) significantly mitigated aggression and stress responsiveness. However, levels of corticosterone in stress in intact aggressive rats of later generations (70s) were lower than in generation 44, which differed little from the corresponding value in “tame” rats, selected in the opposite direction, for the absence of aggressiveness towards humans. The study was conducted with Norway rat populations of the 75th generation of selection for aggressive and tame behavior, respectively. The goal was to find out whether the decrease in stress response in aggressive rats at the current stage of selection was accompanied by a decrease in the influence of handling on aggressiveness. It was found that neonatal handling of aggressive animals caused a significant decrease in aggressiveness, although considerably smaller than in generation 44. In both aggressive and tame rats, the blood corticosterone level at stress was getting back to the basal level for a longer time than in the corresponding control groups. Neonatal handling decreased the amount of mRNA for the glucocorticoid receptor (GR) in the hippocampus of aggressive rats but did not affect significantly the amount of mRNA for the corticotropin-releasing hormone (CRH) in the hypothalamus. However, higher contents of CRH mRNA were recorded in aggressive rats than in tame ones in the control groups. However, no differences in glucocorticoid receptor mRNA  were found between the strains in contrast to earlier generations. It was shown that neonatal handling was beneficial for maternal behavior in tame rats. Thus, the results obtained in the 75th generation of selection indicate that the effect of handling on aggressiveness weakens with decreasing stress responsiveness in aggressive rats. This is likely to be related to the changing amount of GR in the hippocampus and stronger glucocorticoidmediated feedback at the current stage of selection. The minor prolongation of the stress response appears to be related to the stressing component of neonatal handling rather than to changes in maternal care.

One of the species of the family Opisthorchiidae, Opisthorchis felineus (O. felineus), causes severe disturbances in humans and animals, and so it is the subject of important research studies. Two weeks after infection we compared the impact of O. felineus invasion on the changes in blood cells composition, bone marrow hematopoiesis and behavioral startlereflex in inbred C57BL/6 male mice and Syrian hamsters (Mesocricetus auratus). Considerable interspecies differences were revealed for many parameters estimated. It was found that the relative weight of the main organ of the peripheral immune system – spleen, is significantly larger in mice than in hamsters. Moreover, the infection with O. felineus caused a significant enlargement of the spleen only in mice. More pronounced changes in the blood cells composition, which was accompanied by activation of hematopoietic stem cells of myeloid and erythroid set, were determined in hamsters. Blood changes in the response to infection in mice were less severe and were not accompanied by the changes in colony formation. Mouse acoustic startle reaction differed from hamster one too. The expression of the startle reaction and the value of pre-pulse inhibition were discriminated in animals of two species. Infected hamsters had no reaction of habituation  to the sound stimulus. In addition, the maturation of O. felineus worms was faster in hamsters than in mice. Data obtained suggest a greater resistance of mice to O. felineus infection, but do not exclude the availability of mice as a model in the study of processes taking place in the host during the development of experimental opisthorchiasis.

According to the hypothesis of stress relief, a high level of anxiety or stress may cause greater alcohol consumption and alcohol addiction. However, data obtained with experimental animals do not always confirm this statement. Model strains of Norway rats selected for tame and aggressive attitude to humans are some of the models for investigation of relationships among anxiety, the function of the hypothalamus – pituitary – adrenal (HPA) axis, and predisposition to alcohol addiction. Former studies of tame rats, based on the blood levels of corticosterone and adrenocorticotropic hormone (ACTH) in rest and stress, revealed a decrease of the manifestation of anxiety-like behavior and of the HPA function in comparison to aggressive and unselected rats. This work assesses the preferred consumption of ethanol at various concentrations with free access to ethanol and water (two bottlechoice paradigm) and the effect of acute ethanol administration on the behavior of aggressive and tame male rats in an elevated plus maze. After intraperitoneal alcohol administration, tame and aggressive males showed a reduced number of rearings in the center of the elevated plus maze, but the reduction was statistically significant only in the former. It pointed not only to the absence of an anxiolytic action of 12 % ethanol but also to enhancement of anxietylike behavior in tame rats. After seven-day alcohol withdrawal, tame rats showed signs of deprivation, because the alcohol consumption was greater than before the withdrawal. Thus, the difference between tame and aggressive rats in alcohol consumption varies with alcohol concentration. Aggressive males drank more alcohol than water only at the 2 % concentration. Hence, the hypothesis of stress relief is confirmed only for this concentration.

Many serious adverse physiological changes occur during spaceflight, primarily due to microgravity. In search of underlying mechanisms, many experimental tools have been developed, ranging from microgravity modeling on Earth to space flight investigations, part of which is to study the expression of genes and proteins. Unlike bone and muscle tissue, molecular changes in nerve cells during spaceflight are practically unexplored. This review aims at summarizing the recent advances in identifying gene and protein expression changes of nervous system cells under microgravity conditions. To a large extent, this review will focus on the results of the Bion-M1 biosatellite. We have for the first time revealed dopamine and serotonin microgravityresponsive genes (tyrosine hydroxylase, catechol-Omethyltransferase, and D1 receptor in the nigrostriatal system; D1 and 5-HT2A receptors in the hypothalamus; and monoamine oxidase A in the frontal cortex). Decreased genetic control of the dopamine system may contribute to the spaceflight-induced locomotor impairment and dyskinesia described for both animals and humans. Also, the system of neuronal apoptosis is activated under the influence of microgravity as evidenced by changes in the expression of antiapoptotic protein Bcl-XL in the hippocampus and hypothalamus. The long spaceflight produced dysregulation in the genetic control of genes encoding GDNF and CDNF neurotrophic factors. Because they play a crucial role in the protection and maintenance of dopaminergic neurons, reducing their expression may be one of the reasons for the negative impact of spaceflight on the brain dopamine system. Thus, the data obtained from the flight of the Bion-M1 biosatellite for the first time allowed for creating a molecular genetic basis for the currently known neurophysiological mechanisms of adaptation of the central nervous system to the state of weightlessness.

Brain serotonin (5-HT) is known to be involved in the control of a wide range of physiological functions as well as of different kinds of behavior. Such polyfunctionality of 5-HT is mediated by numerous 5-HT receptors. Currently, 14 different 5-HT receptor subtypes expressed in the mammals have been identified. The 5-HT1А receptor is one of the most extensively characterised members of the serotonin receptor family. Increased interest to the 5-HT1А receptor is based on (1) a key role in the autoregulation of the brain serotonergic system due to the postsynaptic and presynaptic localization, (2) a great body of data demonstrating implication of 5-HT1А receptor in the control of various physiological functions (3) involvement of 5-HT1А receptors in the mechanisms of depression, anxiety and suicide. The review describes literature and original data on factors affecting the expression and functional activity of 5-HT1А receptors and the involvement of 5-HT1А receptors in the regulation of normal and pathological behavior. The structure of the 5-HT1А receptor gene is described and new data on the posttranslational regulation of 5-HT1А receptor functional activity are provided. A special focus was given to the interaction between 5-HT1А and 5-HT7 receptors followed by heterodimer formation and the role of heterodimerization in the functional inactivation of the 5-HT1А receptor. The implication of 5-HT1А receptors in the regulation of aggressive behavior, catalepsy, anxiety, depression and hibernation was shown. Special attention is focused on the involvement of 5-HT1А receptors in the regulation of 1) fear-induced aggression towards man – the basis of domestication, 2) intermale aggression underling asocial behavior in men, 3) depression and in the mechanism of antidepressant action. The described data extend the idea on the 5-HT1А receptor as a key player in the brain 5-HT system.

An abnormality in adaptation to negative life events is considered as one of the main causes of the development of depressive symptoms. According to the corticosteroid receptor hypothesis of depression, stress-induced activation of the hypothalamicpituitary- adrenal (HPA) axis plays an important role in the induction of psycho-emotional disturbances. The end products of this axis, glucocorticoids, are involved in the formation of many physiological and behavioral responses to stress. Although the increase in hormone levels following a short-term intervention is directed towards rapid mobilization of the body’s efforts for overcoming potentially dangerous situation, a long-term exposure to stress or glucocorticoids may have negative consequences for mood or behavior. With respect to mechanisms of changing effects of glucocorticoids from protective to damaging, glucocorticoid receptors (GRs) received most attention. These receptors are widely expressed in the brain. They are important regulators of the transcriptional activities of numerous genes, including the gene for such a plasticity-related protein as the brain-derived neurotrophic factor (BDNF) which has been implicated in psychiatric disorders. In addition to direct effects on gene transcription, changes in expression of GR themselves resulting from stress and/or glucocorticoid effects, in turn can modify the functional responses to subsequent stimuli. The purpose of this review was to analyze available literature data on the effects of stress and glucocorticoids on the expression of GR in the hippocampus, which is traditionally considered as the most sensitive to stress brain structure. The review also addresses the implication of GR and BDNF interplay in the pathogenesis of stress-related disorders.

Early life stress events can produce long-lasting changes in neurochemistry and behaviors related to monoamine systems, with increased risks of cardiovascular, metabolic, neuroendocrine, psychiatric disorders, generalized anxiety and depression in adulthood. Tyrosine hydroxylase (TH), the key enzyme for catecholamine synthesis, also plays an important role in the activity of the noradrenergic system and may be a target for glucocorticoids during the perinatal programming of physiological functions and behavior. Administration of hydrocortisone or dexamethasone to female rats on day 20 of pregnancy and to 3-day-old neonatal pups significantly increased TH mRNA levels (real-time PCR) and enzyme activity as well as protein levels determined by ICH in the locus coeruleus. Moreover, our treatment led to increase in TH mRNA levels in 25- and 70-day-old animals, as well as an increase in enzyme activity in the brainstem and cerebral cortex of adult rats. The long-term changes in TH expression are limited by the perinatal period of development. Administration of hormones on day 8 of life was not accompanied by changes in TH mRNA levels or enzyme activity. Glucocorticoids use several mechanisms to bring about transactivation or transrepression of genes. The main mechanism includes direct binding of the hormone-activated GRs to glucocorticoid responsive elements (GREs) in the promoter region of genes. However, despite optimistic claims made the classical GRE was not found in the TH gene promoter. Protein – protein interactions between hormone-activated GR and other transcription factors, for example, AP-1, provide an additional mechanism for the effects of glucocorticoids on gene expression. An important feature of this mechanism is its dependence on the composition of proteins formed by AP-1. Hormone-activated GRs are able to enhance gene expression when AP-1 consists of the Jun / Jun homodimer, but do not do that when AP-1 appears as the Jun / Fos heterodimer. Furthermore, as has been shown recently, the GRE / AP-1 composite site is the major site of interaction of glucocorticoids with  the TH gene in the pheochromocytoma cell line. Ontogenetic variation in the expression of Fos and Jun family proteins, which affects their ratio, can be one of the reasons for the TH gene regulation by glucocorticoids at near-term fetuses and neonates. However, to date this hypothesis has been supported only by in vitro data, and the existence of this mechanism in in vivo conditions needs to be explored in further studies.

Early postnatal proinflammatory stress provokes behavioral impairments in adulthood; however, underlying mechanisms are still elusive. Brain-derived neurotrophic factor (BDNF) plays a crucial role in neuroplastic changes in health as well as at pathology. The BDNF gene is transcribed to exon-specific mRNAs and the pattern of their expression depends on stimulus. We suggest that disturbances of exonspecific BDNF mRNA expression in the brain regions after stress induced by proinflammatory stimuli in early postnatal period could be one of the underlying mechanisms of consequent behavioral impairments. Thus, the aim of the study was to investigate the effects of proinflammatory stress in early postnatal ontogeny on the expression of BDNF and the patterns of expression of the BDNF gene in the neocortex and hippocampus of prepubertal male rats. The proinflammatory stress was induced by subcutaneous administration of bacterial lipopolysaccharide (LPS) to rat pups on postnatal days 3 and 5, while BDNF expression was analyzed in 36-day-old rats. BDNF polypeptide concentration was estimated by means of an enzyme-linked immunosorbent assay, while quantitative polymerase chain reaction followed by reverse transcription was used to detect exon-specific BDNF mRNA expression. The levels of BDNF and transcripts, containing common exon IX were similar in the control and LPS-treated rats. In the rats treated with LPS, the level of BDNF mRNA, containing exon IV, was lower in the neocortex, but not in the hippocampus. No changes in the expression of the transcripts containing exons I and VI were observed in any brain structure studied. We suggest that specific alterations in BDNF expression may be involved in the susceptibility to the development of behavioral impairments of animals subjected to early proinflammatory stress.

Neurochemical mechanisms of initiation and expression of epileptic seizures are poorly explored, and there are no published data that could demonstrate the functional state of the neuromediator systems at the initial state of seizure in the animals genetically prone to seizure. In the current work, we studied the role of extracellular signal-regulated kinase (ERK1/2) in the regulation of the nigrostriatal glutamate, GABA and dopamine neurons of Krushinsky – Molodkina rats at clonus-tonus and ataxia stages of audiogenic seizure. We demonstrated upregulation of ERK1/2 activity upon audio stimulation which was accompanied by increased activation of Synapsin I in the striatum and substantia nigra in comparison to intact Krushinsky – Molodkina rats. The observed exocytosis activation led to secretion of glutamate in the striatum and, as a result, to stimulation of seizures. However, at clonus-tonus stage in the striatum we revealed the changes that could participate in further inhibition of seizure activity, such as increased phosphorylation of tyrosine hydroxylase upon increased ERK1/2 activity followed by activation of dopamine release in the pars compacta of the substantia nigra. At the same time, enhanced D2 and increased D1 dopamine receptor contents were observed. These data revealed attenuation of direct (pro-seizure) and indirect (anti-seizure) pathways of the regulation of the substantia nigra GABA neurons. We demonstrated activation of GABA in the substantia nigra pars reticulate, which probably results in the inhibition of glutamate neurons of the thalamus and could be one of the mechanisms inhibiting seizure activity during ataxia.

The neuropeptide oxytocin (OT) and its homologues are produced in specialized neurons located in Vertebrates exclusively in a deep and evolutionarily old part of the forebrain, the hypothalamus. The axons of OT neurons form the classical hypothalamic-neurohypophyseal tract terminating on blood vessels of the neurohypothysis to release OT into the systemic blood circulation. However, as was recently demonstrated in mammals, collaterals of OT axons concomitantly project to various forebrain regions to modulate the activity of local networks. At the behavioral level, OT facilitates intraspecific social contacts in mammals via various mechanisms ranging from the suppression of neuroendocrine stress responses to the direct OT action on neurons of socially relevant brain regions. Recent reports indicated possible contribution of OT to the formation of the social bond between domesticated mammals (dog, sheep, cattle) and humans. Indeed, social interaction between humans and a domesticated animal resulted in the elevation of peripheral OT levels (in blood, saliva or urine) and, in congruence, exogenous (intranasal) OT application led to more frequent contacts between the owner and the domesticated animal. It has been known for decades that domesticated animals exhibit profound socio-communicative abilities accompanied by suppressed aggression and stress responsiveness. These peculiarities of their behavior and physiology may be influenced by the activity of the central OT system. Therefore, in the present mini-review we focus on the role of OT in the orchestration of distinct forms of social behavior, including the monogamous bond, maternal care, social memory and recognition, aggression, and anxiety. As a conclusion, we propose possible directions for exploration of the OT contribution to empathy between humans and domesticated animals, which was likely established in the course of their co-evolution during last 10.000– 15.000 years.

The transgenic mouse technology is widespread, however, untill now 22.0 % of tested null mutations was found to be lethal. The complete lack of vasopressin (AVP) resulted also in preweaning lethality. It is surprising take into consideration the viability of the AVP mutant Brattleboro rats. Thus, AVP is essential for survival, but which of its ubiquiter role is the most important. AVP exerts its effect through specific plasma membrane receptors. V1a receptors can induce vasoconstriction maintaining blood pressure during hypovolemia. The V1b receptor on the anterior pituitary has a role in stress adaptation. The V2 subtype is located in the kidney and contributes to the antidiuresis. The avp gene consists of a signal peptide, AVP, neurophysin 2 and a C-terminal glycopeptide. The naturally occuring AVP-deficient Brattleboro rat has a framshift mutation in the neurophysin portion resulting in cental diabetes insipidus. In its hypothalamus AVP is not produced, while in certain peripheral tissues it may be expressed, suggesting the existence of a different synthetic pathway. The avp knockout mice can also be produced, they will be born, but without peripheral AVP administration they will not survive. Comparing available knockout models we can conclude that the combined V1a and V2 receptor mediated effects, namely hypotension and water lost together may led to lethality. As in Brattleboro and targetted knockout mice the local synthesis of AVP in the heart can be maintained and AVP can be released into the general circulation. Thus, in these animals vasoconstriction can compensate the hypovolemia.

In mammals, arginine-vasopressin (AVP) is a major hormone involved in the regulation of renal water reabsorption, acting via an increase in the osmotic permeability of the collecting duct epithelium. The AVP-induced intracellular events include, as an essential step, the trafficking of the vesicles containing the water channels, aquaporin-2, to the apical plasma membrane of the collecting duct principal cells. The interstitium of the renal inner medulla contains abundant linear negatively charged glycosaminoglycan hyaluronan (HA), which affects the water flow depending on their polymeric state. Using real-time RT-PCR, we tested the assumption that the renal hyaluronan may be involved in the longterm vasopressin effect on water reabsorption. The expression of the genes encoding hyaluronan synthase-2 (Has2) and hyaluronidase-1, 2 (Hyal1, Hyal2) in the kidneys of Wistar Albino Glaxo (WAG) was studied. Has2 mRNA content was the highest in the kidney papilla of the hydrated rats. The V2 receptor-selective vasopressin analog dDAVP (100 μg/kg bw, ip, twice a day for 2 days) induced a considerable decrease in Has2 mRNA content in the papilla with less pronounced changes in the cortex. In contrast to Has2, dDAVP treatment caused a significant increase in Hyal1 and Hyal2 mRNA content in the renal papilla. There was a good fit between Hyal1 and Hyal2 transcriptional level and changes in hyaluronidase activity in the renal tissue. It was suggested that vasopressin is able to inhibit the synthesis of hyaluronan and concomitantly promotes its degradation in the renal papilla interstitium, thereby facilitating water flow between elements of the renal countercurrent system. The implications for this effect are discussed in the context of the literature data.

The growth dynamics of transplantable Walker 256 carcinosarcoma was investigated in rats modeling inherited systemic pathological processes. Hypothalamic diabetes insipidus is developing in Brattleboro rats on the background of total vasopressin absence in the blood. Regulation of water-electrolytic metabolism is disturbed due to hormonal disbalance. ISIAH rats are carriers of inherited stress-induced arterial hypertension. Vascular rigidity is accompanied by additional pleiotropic effects. The experiments have been carried out on inbred Brattleboro and ISIAH rats, and their hybrids segregated from (ISIAH × Brattleboro) F1 × Brattleboro mating. The mutant vasopressin gene di (diabetes insipidus) and fur painting genes, albino (C) and hooded (h), localized in three different linkage groups, were used as genetic markers of progeny splitting. Alternative pairs of traits were: daily water consumption above 45 % or lower than 20 % of body weight – for the vasopressin locus; total white or other color of fur – for the albino locus; presence or absence of unevenness in fur painting – for the hooded locus. It has been found that there are only two types of growth dynamics of grafted tumor. In the rats of the inbred Brattleboro line and in the didi homozygotes, which were segregated from analytical mating (ISIAH × Brattleboro) F1 × Brattleboro, tumor began to regress and diminished until absolute disappearance after some initial growing. Heterozygous offspring di+ and parental ISIAH rats with the normal vasopressin genotype (++) showed permanent tumor growth until lethal injury. It was found that tumor regression demonstrates concordance exclusively to the didi genotype, segregation of this feature does not depend on the genotype of the albino or hooded loci. Alternative to tumor regression, permanent growth of tumor is observed in all rats having at least one normally expressed vasopressin gene.

The common questions in the design of the highthroughput sequencing experiments using RNA-Seq or Ribo-Seq methods are reviewed. The ENCODE guidelines (2011) as well as the recently published advances in the design of the studies of mammalian, animal and plant transcriptomes are also summarized in this review. The optimal limit of the sequencing depth does exist for the identification of almost all actively transcribed genes. This limit depends on the transcriptome size in the biological object studied. Additional sequencing does not provide any substantial additional information about the transcriptome complexity. For mammals, the optimal limit of the sequencing depth for the identification of the actively transcribed genes is equal to ~ 2 × 109 bp per biological sample. For other species, the optimal limit of the sequencing depth per biological sample is determined similarly for mammals; however, the transcriptome size and the mean RNA content in the studied object should be taken into account, in comparison to the mammalian transcriptomes. The discovery of differentially expressed genes, as well as the identification of splicing sites in the mRNA could be enhanced by increasing the number of biological samples analyzed per each experimental group. The minimal number of biological replicates per experimental group is equal to 2. However, the optimal number of biological replicates per experimental group is equal to 5–8 (similar to the experiments quantifying the expression of single genes by qRT-PCR). For the transcriptome studies, it is recommended to use the sequencing technologies that have the accuracy of sequencing ≥ 0.999 per bp. For RNASeq, it is also recommended to use the technologies that are able to produce reads equal to or larger than 75 bp, to minimize the cost of the effective identification of the sequences. The relative cost for the sequencing of the control samples could be reduced by increasing the number of experimental groups in the experiment or by combining several independent experiments with similar control groups. The present notes could be utilized during the design step in the experimental studies devoted to the research of transcriptomes.

Optogenetics, that is, the control of cell activity using light-sensitive ion channels opsins with light of a specific wavelength, is increasingly being used to study activities and functions of neurons. Expression of opsins in the cell membrane, followed by the acquisition by the cell of the sensitivity to light is achieved by means of viral vectors, often created on the basis of lentiviral or adeno-associated (AAV) viruses bearing the nucleotide sequence encoding the photo-channel proteins. Inclusion of the cell-specific promoter of interest into the transgene-expression cassette allows opsin to be produced only in the target cells. The aim of this work was to briefly describe the optogenetic method, as well as to analyze the possibility to use administration of viral vectors into the brain of neonatal animals to study the function of neurons in vivo during subsequent periods of development. In this analysis, 3-day-old rat pups received intracerebroventricular injections of optovector (pAAV-CAMKIIa-ChR2h134-YFP), coding for a photo channel, which activates neurons, and the yellow fluorescent marker protein under the CAMKIIa promoter specific for glutamatergic neurons under cold anesthesia. The peak expression of the transferred gene is usually achieved at week 3–5 after the transfer of the vector, which is what was also observed in our experiments. Stimulation of the hippocampal neurons with blue light in the 20-day-old animals, to which opto-vector was transferred at the 3rd day of life, increased the discharge activity of these neurons. This light stimulation increased expression of the recognized marker of neuronal activation protein c-Fos in these photosensitive cells too. The same experiments with older animals, 60 days after the neonatal opto-channel gene transfer, revealed no noticeable expression of this channel or photoactivation of target neurons of the hippocampus. Thus, neonatal administration of a viral vector carrying an opto-channel gene is suitable for the study of brain neurons in rats of juvenile age, and requires additional control for gene expression during subsequent periods of development.

Epigenetic modifications are studied intensively to understand mechanisms of long-term memory. We have shown that histone H3 methylation is important for the defense reflexes formation in the mollusk Helix lucorum. We suggested that these epigenetic modifications are controlled by facilitatory and inhibitory pathways involved in the long-term memory formation. Serotonin and neuropeptide FMRFamide play opposite roles in the formation of defensive reflexes. Serotonin strengthens synaptic connections between neurons of the network, and FMRFamid is an inhibitory transmitter leading to long-term depression. To study the epigenetic regulation of the processes involved in the long-term memory formation, we performed comparative studies on the serotonin and FMRFamide effects on histone H3 methylation in the CNS of the Helix. We found that the incubation of the CNS with serotonin induces methylation of histone H3 at both activating (Н3K4me3) and inhibitory (Н3K9me2) sites, while incubation with FMRFamide has an opposite effect reducing methylation of histone H3 in the subesophageal complex of ganglia, important for defensive behaviour. We observed a different methylation pattern of histone H3 in the cerebral ganglia involved in signal processing of food stimuli, where serotonin did not affect the methylation of histone H3 at the activator site and reduced methylation at the inhibitory site, while FMRFamid had no effect on methylation. The data indicate that the facilitatory and inhibitory processes mediated by serotonin and FMRFamide can interact at the epigenetic level, through histone H3 methylation by activating or inhibiting it, respectively. This may underlie the convergence of the activator and inhibitory pathways involved in the long-term memory formation and underlie following regulation of the expression of genes involved in long-term plasticity.