Modulation of GABA release by 5-HT1B receptors: An interplay with AMPA-receptors and voltage-gated Ca2+ channels.

Obesity has become a worldwide health challenge and commonly results from the intake of more calories than the body requires. The brain represents the master controller of food intake and as such has been the target of obesity medications. However, key mechanisms of druggable targets remain to be defined. Neurons within the arcuate nucleus of the hypothalamus co-expressing neuropeptide Y (NPY), agouti-related protein (AgRP) and GABA (NAG) are fundamental stimulators of hunger and food intake. NAG neurons also inhibit local satiety-promoting pro-opiomelanocortin (POMC) neurons. Agonists of the 1B subtype of metabotropic serotonin receptor (5-HT1BR) reduce food intake in part through the inhibition of hunger-promoting NAG neurons. We first confirmed that 5-HT1BR activation suppressed intake of a palatable Western diet in a mouse model of common dietary-induced obesity and genetically prone obesity. Next, we combined several electrophysiological approaches to analyse the effect of 5-HT1BRs in NAG neuron cell activity and GABA release. 5-HT1BR activation reduced NAG neuron action potential frequency and neurotransmitter release. We found that 5-HT1BR impact on GABA release from NAG neurons is mediated through voltage-gated Ca2+ channels with a critical input from glutamate receptors of AMPA subtype (AMPARs). As a fundamental outcome, this type of interplay provides an uncommon example of metabotropic action of AMPARs which regulates inhibitory signalling due to modulation of GABA release. As a translational outcome, our results provide a key mechanism through which 5-HT1BR drugs inhibit appetite-stimulating neurons within the brain to suppress food intake. This article is part of the Special Issue on "Ukrainian Neuroscience".

NEUROTIC CONDITIONS: PROBLEM, DIAGNOSIS, CORRECTION BY COGNITIVE-BEHAVIOR THERAPY.

OBJECTIVE: The aim: To identify the relationship between neurotic states and hardiness as an indicator of mental health, to explore the possibility of using the cognitive-behavior therapy techniques to correct neurotic states in young people. PATIENTS AND METHODS: Materials and methods: The methods "Clinical questionnaire for the detection and evaluation of neurotic conditions" (K. Yakhin, D. Mendelevich) and "Hardiness Survey" (S. Muddi, adapted by D. Leontev, O. Rasskazova) were used for diagnosis. Wilcoxon test was used to determine changes in the manifestations of neurotic states in the conditions "before" and "after" the application of cognitive-behavior therapy techniques. Correlation analysis was used also to distinguish the relationship between neurotic states, hardiness and its components. RESULTS: Results: It has been identified that various neurotic states are differently related to hardiness as an indicator of mental and social health. The level of anxiety and obsessivephobic disorders has inverse negative relationship with general level of hardiness (r = -0.31 and r = -0.34), but the level of asthenia has a positive connection with this indicator (r = 0.49). The level of neurotic anxiety is inversely related with the level of personal involvement in life (r = -0.27). The effectiveness of CBT techniques (psycho-education, distancing, cognitive reassessment) for the correction of neurotic states, namely: anxiety (p <0.01) and hysterical reaction type (p <0.01) was proved. CONCLUSION: Conclusions: Neurotic states are correlated with level of hardiness (an indicator of mental and social health) and personal involvement in life. The correction of neurotic states can be effectively carried out by means of CBT.

THE INFLUENCE OF UNHEALTHY NEUROTICISM ON THE PECULIARITIES OF PERSONAL DECISION MAKING.

OBJECTIVE: The aim: To determine the influence of unhealthy neuroticism (the high level of personal neuroticism) on the properties of the decision-making process, to identify the differences in the decision-making process features of persons with high and low levels of neuroticism. PATIENTS AND METHODS: Materials and methods: A comparative design was used with two contrasting groups, which differed in the level of neuroticism. Causal relationships were defined using one-way analysis of variance (ANOVA). The methods «Diagnosis of the neurotic personality tendency" (L. Vasserman), "Diagnosis of decision-making features" (D. Myroshnyk, O. Savchenko), "Locus of control" (O. Ksenofontova) were used for diagnosis. RESULTS: Results: It was identified that individuals with a high level of neurotic personality tendency have exhibited less self-control in the decision-making process (p <0.01), have formed a pessimistic expectations of the ways in which decisions should be fulfilled (p <0.01). A high level of neurotic personality tendency has occurred mostly in students with a high level of external locus of control (p <0.01), a low assessment of self-competence (p <0.01), low internality in the field of interpersonal relations (p <0.05), unformed willingness to overcome difficulties (p <0.05). The level of neuroticism is an important factor of the peculiarities of decision-making process (self-control (p <0.001) and optimistic expectations (p <0.02)). The general level of internality has determined the level of neurotic personality tendency (p <0.02). CONCLUSION: Conclusions: Unhealthy neuroticism, which manifests itself in a high level of neurotic personality tendency, is a risk factor of mental health, and it prevents timely make appropriate decisions. The high level of external locus of control mediately (through increasing the level of neurotic personality tendency) affects the procedural and effective properties of the decision-making process.