Neuroprotective and Neurite Outgrowth Stimulating Effects of New Low-Basicity 5-HT Receptor Agonists: In Vitro Study in Human Neuroblastoma SH-SY5Y Cells.

There is some evidence that the serotonin receptor subtype 7 (5-HT) could be new therapeutic target for neuroprotection. The aim of this study was to compare the neuroprotective and neurite outgrowth potential of new 5-HT receptor agonists (AH-494, AGH-238, AGH-194) with 5-CT (5-carboxyamidotryptamine) in human neuroblastoma SH-SY5Y cells. The results revealed that 5-HT mRNA expression was significantly higher in retinoic acid (RA)-differentiated cells when compared to undifferentiated ones and it was higher in cell cultured in neuroblastoma experimental medium (DMEM) compared to those placed in neuronal (NB) medium.

Non-motor symptoms associated with progressive loss of dopaminergic neurons in a mouse model of Parkinson's disease.

Parkinson's disease (PD) is characterized by three main motor symptoms: bradykinesia, rigidity and tremor. PD is also associated with diverse non-motor symptoms that may develop in parallel or precede motor dysfunctions, ranging from autonomic system dysfunctions and impaired sensory perception to cognitive deficits and depression. Here, we examine the role of the progressive loss of dopaminergic transmission in behaviors related to the non-motor symptoms of PD in a mouse model of the disease (the TIF-IA strain).

Prosocial behavior, social reward and affective state discrimination in adult male and female mice.

Prosocial behavior, defined as voluntary behavior intended to benefit another, has long been regarded as a primarily human characteristic. In recent years, it was reported that laboratory animals also favor prosocial choices in various experimental paradigms, thus demonstrating that prosocial behaviors are evolutionarily conserved. Here, we investigated prosocial choices in adult male and female C57BL/6 laboratory mice in a task where a subject mouse was equally rewarded for entering any of the two compartments of the experimental cage, but only entering of the compartment designated as "prosocial" rewarded an interaction partner.

Psychological interventions countering misinformation in social media: A scoping review.

Introduction: The rise of social media users and the explosive growth in misinformation shared across social media platforms have become a serious threat to democratic discourse and public health. The mentioned implications have increased the demand for misinformation detection and intervention. To contribute to this challenge, we are presenting a systematic scoping review of psychological interventions countering misinformation in social media.

Loss of mu and delta opioid receptors on neurons expressing dopamine receptor D1 has no effect on reward sensitivity.

Opioid signaling controls the activity of the brain's reward system. It is involved in signaling the hedonic effects of rewards and has essential roles in reinforcement and motivational processes. Here, we focused on opioid signaling through mu and delta receptors on dopaminoceptive neurons and evaluated the role these receptors play in reward-driven behaviors.

Chemical puzzles in the search for new, flexible derivatives of lurasidone as antipsychotic drugs.

In the pharmacotherapy of schizophrenia, there is a lack of effective drugs, and currently used agents cause a large number of side effects. The D, 5-HT, 5-HT receptors are among the most important receptor targets in the treatment of schizophrenia, but antagonism at 5-HT and 5-HT receptors may bring about additional improvement of cognitive functions. However, doubt exists regarding the importance of 5-HTR in the pharmacotherapy.

The role of magnesium and zinc in depression: similarities and differences.

Antidepressant therapy exhibits low clinical efficacy and produces a variety of unwanted side effects. Therefore, the search for more effective antidepressants is still in progress. Antidepressant properties of magnesium and zinc have been demonstrated in animal screen tests/models and clinical studies.

Ablation of NMDA receptors in dopamine neurons disrupts attribution of incentive salience to reward-paired stimuli.

Midbrain dopamine (DA) neurons play a crucial role in the formation of conditioned associations between environmental cues and appetitive events. Activation of N-methyl-d-aspartate (NMDA) receptors is a key mechanism responsible for the generation of conditioned responses of DA neurons to reward cues. Here, we tested the effects of the cell type-specific inactivation of NMDA receptors in DA neurons in adult mice on stimulus-reward learning.

Selective Effects of the Loss of NMDA or mGluR5 Receptors in the Reward System on Adaptive Decision-Making.

Selecting the most advantageous actions in a changing environment is a central feature of adaptive behavior. The midbrain dopamine (DA) neurons along with the major targets of their projections, including dopaminoceptive neurons in the frontal cortex and basal ganglia, play a key role in this process. Here, we investigate the consequences of a selective genetic disruption of NMDA receptor and metabotropic glutamate receptor 5 (mGluR5) in the DA system on adaptive choice behavior in mice.

Expression of alternatively spliced variants of the Dclk1 gene is regulated by psychotropic drugs.

Background: The long-term effects of psychotropic drugs are associated with the reversal of disease-related alterations through the reorganization and normalization of neuronal connections. Molecular factors that trigger drug-induced brain plasticity remain only partly understood. Doublecortin-like kinase 1 (Dclk1) possesses microtubule-polymerizing activity during synaptic plasticity and neurogenesis.

Decoding the transcriptional programs activated by psychotropic drugs in the brain.

Analysis of drug-induced gene expression in the brain has long held the promise of revealing the molecular mechanisms of drug actions as well as predicting their long-term clinical efficacy. However, despite some successes, this promise has yet to be fulfilled. Here, we present an overview of the current state of understanding of drug-induced gene expression in the brain and consider the obstacles to achieving a robust prediction of the properties of psychoactive compounds based on gene expression profiles.

Lactose esters: synthesis and biotechnological applications.

Biodegradable nonionic sugar esters-based surfactants have been gaining more and more attention in recent years due to their chemical plasticity that enables the various applications of these molecules. In this review, various synthesis methods and biotechnological implications of lactose esters (LEs) uses are considered. Several chemical and enzymatic approaches are described for the synthesis of LEs, together with their applications, i.

CREB activity in dopamine D1 receptor expressing neurons regulates cocaine-induced behavioral effects.

It is suggested that striatal cAMP responsive element binding protein (CREB) regulates sensitivity to psychostimulants. To test the cell-specificity of this hypothesis we examined the effects of a dominant-negative CREB protein variant expressed in dopamine receptor D1 (D1R) neurons on cocaine-induced behaviors. A transgenic mouse strain was generated by pronuclear injection of a BAC-derived transgene harboring the A-CREB sequence under the control of the D1R gene promoter.

A model of alcohol drinking under an intermittent access schedule using group-housed mice.

Here, we describe a new model of voluntary alcohol drinking by group-housed mice. The model employs sensor-equipped cages that track the behaviors of the individual animals via implanted radio chips. After the animals were allowed intermittent access to alcohol (three 24 h intervals every week) for 4 weeks, the proportions of licks directed toward bottles containing alcohol were 50.

Addictive drugs and plasticity of glutamatergic synapses on dopaminergic neurons: what have we learned from genetic mouse models?

Drug-induced changes in the functional properties of neurons in the mesolimbic dopaminergic system are attractive candidates for the molecular underpinnings of addiction. A central question in this context has been how drugs of abuse affect synaptic plasticity on dopaminergic cells in the ventral tegmental area. We now know that the intake of addictive drugs is accompanied by a complex sequence of alterations in the properties of excitatory synapses on dopaminergic neurons, mainly driven by signaling and redistribution of NMDA- and AMPA-receptors.

Novelty-seeking behaviors and the escalation of alcohol drinking after abstinence in mice are controlled by metabotropic glutamate receptor 5 on neurons expressing dopamine d1 receptors.

Background: Novel experiences activate the brain's reward system in a manner similar to drugs of abuse, and high levels of novelty-seeking and sensation-seeking behavior have been associated with increased susceptibility to alcohol and drug abuse. Here, we show that metabotropic glutamate receptor 5 (mGluR5) signaling on dopaminoceptive neurons is necessary for both novelty-seeking behavior and the abstinence-induced escalation of alcohol drinking.

Methods: Mice harboring a transgene expressing microRNA hairpins against mGluR5 messenger RNA under the control of the D1 dopamine receptor gene promoter (mGluR5(KD-D1)) were tested in a battery of behavioral tests measuring learning abilities, anxiety levels, reactions to novelty, operant sensation seeking, and alcohol sensitivity.

Glutamate input to noradrenergic neurons plays an essential role in the development of morphine dependence and psychomotor sensitization.

The brain's noradrenergic system is involved in the development of behaviours induced by drugs of abuse, e.g. dependence and withdrawal, and also reward or psychomotor effects.

Synthesis and serotonin receptor activity of the arylpiperazine alkyl/propoxy derivatives of new azatricycloundecanes.

A set of 36 arylpiperazine derivatives with two novel complex terminal imide fragments, 8,11-dimethyl-3,5-dioxo-4-azatricyclo[5.2.2.

New imide 5-HT1A receptor ligands - modification of terminal fragment geometry.

Two sets of new o-methoxyphenylpiperazine (MPP; series a) and 1,2,3,4-tetrahydroisoquinoline (THIQ; series b) derivatives, containing various imide moieties derived from NAN190, were synthesized and evaluated in vitro for their ability to bind to the serotonin 5-HT(1A) and 5-HT(2A) receptors. All new derivatives from series a demonstrated high 5-HT(1A) affinities, whereas THIQ analogues were much less active. With respect to 5-HT(2A) receptors, three MPP derivatives presented moderate activity but the rest of the investigated compounds were practically inactive.

Conformational fluctuations versus constraints in amino acid side chains: the evolution of information content from free amino acids to proteins.

Like all other complex biological systems, proteins exhibit properties not found in free amino acids (i.e., emergent properties).

Conformational constraints on side chains in protein residues increase their information content.

Like all other complex biological systems, proteins exhibit properties not seen in free amino acids (i.e., emergent properties).