Deep learning algorithms reveal increased social activity in rats at the onset of the dark phase of the light/dark cycle.

The rapid decrease of light intensity is a potent stimulus of rats' activity. The nature of this activity, including the character of social behavior and the composition of concomitant ultrasonic vocalizations (USVs), is unknown. Using deep learning algorithms, this study aimed to examine the social life of rat pairs kept in semi-natural conditions and observed during the transitions between light and dark, as well as between dark and light periods.

Unraveling psilocybin's therapeutic potential: behavioral and neuroplasticity insights in Wistar-Kyoto and Wistar male rat models of treatment-resistant depression.

Rationale: Our study aimed to unravel the unknown mechanisms behind the exceptional efficacy of Psilocybin (PSI) in treating treatment-resistant depression (TRD). Focusing on Wistar-Kyoto (WKY) rats with a TRD phenotype and Wistar (WIS) rats as a normative comparison, we investigated behavioral and neuroplasticity-related responses to PSI, striving to shed light on the distinctive features of its antidepressant effects.

Objectives: We set out to assess the behavioral impact of acute and prolonged PSI administration on WKY and WIS rats, employing Novel Object Recognition (NORT), Social Interaction (SI), and Forced Swimming Test (FST).

Effects of ketamine on rat social behavior as analyzed by DeepLabCut and SimBA deep learning algorithms.

Traditional methods of rat social behavior assessment are extremely time-consuming and susceptible to the subjective biases. In contrast, novel digital techniques allow for rapid and objective measurements. This study sought to assess the feasibility of implementing a digital workflow to compare the effects of ()-ketamine and a veterinary ketamine preparation Vetoquinol (both at 20 mg/kg) on the social behaviors of rat pairs.

Pro-social and pro-cognitive effects of LIT-001, a novel oxytocin receptor agonist in a neurodevelopmental model of schizophrenia.

Social and cognitive dysfunctions are the most persistent symptoms of schizophrenia. Since oxytocin (OXT) is known to play a role in social functions and modulates cognitive processes, we investigated the effects of a novel, nonpeptide, selective OXT receptor agonist, LIT-001, in a neurodevelopmental model of schizophrenia. Administration of methylazoxymethanol acetate (MAM; 22 mg/kg) on the 17th day of rat pregnancy is known to cause developmental disturbances of the brain, which lead to schizophrenia-like symptomatology in the offspring.

5-HT receptor antagonists. Design, synthesis, and structure-activity relationship of substituted 2-(1-methyl-4-piperazinyl)pyridines.

In this study, we present the discovery and pharmacological characterization of a new series of 6-piperazinyl-7-azaindoles. These compounds demonstrate potent antagonism and selectivity against the 5-HT receptor. Our research primarily focuses on optimizing the lead structure and investigating the structure-activity relationship (SAR) of these compounds.

Impact of the Substitution Pattern at the Basic Center and Geometry of the Amine Fragment on 5-HT and DR Affinity in the 1-Pyrrolo[3,2-]quinoline Series.

Salt bridge (SB, double-charge-assisted hydrogen bonds) formation is one of the strongest molecular non-covalent interactions in biological systems, including ligand-receptor complexes. In the case of G-protein-coupled receptors, such an interaction is formed by the conserved aspartic acid (D3.32) residue and the basic moiety of the aminergic ligand.

Maternal immune activation affects socio-communicative behavior in adult rats.

A wide body of evidence suggests a relationship between maternal immune activation (MIA) and neurodevelopmental disorders such as autism spectrum disorder (ASD). Since social and communicative deficits are included in the first diagnostic criterion of ASD, we aimed to characterize socio-communicative behaviors in the MIA model based on prenatal exposure to poly(I:C). Our previous studies demonstrated impaired socio-communicative functioning in poly(I:C)-exposed adolescent rats.

The Effects of Positive Allosteric Modulators of α7-nAChR on Social Play Behavior in Adolescent Rats Prenatally Exposed to Valproic Acid.

There is still no effective treatment that addresses the core symptoms of autism spectrum disorders (ASD), including social and communication deficits. A comprehensive body of evidence points to the cholinergic system, including alpha7-nicotinic acetylcholine receptors (α7-nAChRs), as a potential target of pharmacotherapy. A promising approach is based on positive allosteric modulators (PAMs) of these receptors due to their advantages over direct agonists.

Comparison of iSeq and MiSeq as the two platforms for 16S rRNA sequencing in the study of the gut of rat microbiome.

Amplicon-based next-generation sequencing (NGS) of the 16S ribosomal RNA (16S) regions is a culture-free method used to identify and analyze Procaryota occurring within a given sample. The prokaryotic 16S rRNA gene contains conserved regions and nine variable regions (V1-V9) frequently used for phylogenetic classification of genus or species in diverse microbial populations. This work compares the accuracy and efficacy of two platforms, iSeq and MiSeq from Illumina, used in sequencing 16S rRNA.

Effects of ketamine optical isomers, psilocybin, psilocin and norpsilocin on time estimation and cognition in rats.

Rationale: Ketamine and psilocybin belong to the rapid-acting antidepressants but they also produce psychotomimetic effects including timing distortion. It is currently debatable whether these are essential for their therapeutic actions. As depressed patients report that the "time is dragging," we hypothesized that ketamine and psilocybin-like compounds may produce an opposite effect, i.

Astroglia in Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is an umbrella term encompassing several neurodevelopmental disorders such as Asperger syndrome or autism. It is characterised by the occurrence of distinct deficits in social behaviour and communication and repetitive patterns of behaviour. The symptoms may be of different intensity and may vary in types.

Structure-Based Design and Optimization of FPPQ, a Dual-Acting 5-HT and 5-HT Receptor Antagonist with Antipsychotic and Procognitive Properties.

In line with recent clinical trials demonstrating that ondansetron, a 5-HT receptor (5-HTR) antagonist, ameliorates cognitive deficits of schizophrenia and the known procognitive effects of 5-HT receptor (5-HTR) antagonists, we applied the hybridization strategy to design dual-acting 5-HT/5-HTR antagonists. We identified the first-in-class compound , which behaves as a 5-HTR antagonist and a neutral antagonist 5-HTR of the Gs pathway. shows selectivity over 87 targets and decent brain penetration.

Repeated treatment with alpha 7 nicotinic acetylcholine receptor ligands enhances cognitive processes and stimulates Erk1/2 and Arc genes in rats.

The α7 nicotinic acetylcholine receptor (α7 nAChR) is a potential target for the treatment of cognitive decline in patients with schizophrenia, Alzheimer's disease, and attention-deficit/hyperactivity disorder. Here we examined the promnesic activity of the α7 nAChR agonist (A582941), the type I (CCMI), and the type II (PNU120596) positive allosteric modulators (PAMs) in rats following single and repeated (once daily for seven days) treatment. To determine the neuronal mechanisms underlying the procognitive activity of the tested compounds, levels of the extracellular signal-regulated kinases (Erk1/2) and the activity-regulated cytoskeleton-associated protein (Arc) mRNAs were assessed in the frontal cortical and hippocampal brain regions.

The Effect of Maternal Immune Activation on Social Play-Induced Ultrasonic Vocalization in Rats.

Prenatal maternal infection is associated with an increased risk of various neurodevelopmental disorders, including autism spectrum disorders (ASD). Maternal immune activation (MIA) can be experimentally induced by prenatal administration of polyinosinic:polycytidylic acid (poly I:C), a synthetic viral-like double-stranded RNA. Although this MIA model is adopted in many studies, social and communicative deficits, included in the first diagnostic criterion of ASD, are poorly described in the offspring of poly(I:C)-exposed dams.

2-Phenyl-1-pyrrole-3-carboxamide as a New Scaffold for Developing 5-HT Receptor Inverse Agonists with Cognition-Enhancing Activity.

Serotonin type 6 receptor (5-HTR) has gained particular interest as a promising target for treating cognitive deficits, given the positive effects of its antagonists in a wide range of memory impairment paradigms. Herein, we report on degradation of the 1-pyrrolo[3,2-]quinoline scaffold to provide the 2-phenyl-1-pyrrole-3-carboxamide, which is devoid of canonical indole-like skeleton and retains recognition of 5-HTR. This modification has changed the compound's activity at 5-HTR-operated signaling pathways from neutral antagonism to inverse agonism.

Chronic Lorcaserin Treatment Reverses the Nicotine Withdrawal-Induced Disruptions to Behavior and Maturation in Developing Neurons in the Hippocampus of Rats.

Preclinical data have shown that treatment with serotonin (5-HT) receptor agonists inhibits the behavioral effects of nicotine, including self-administration, reinstatement, and locomotor responses to nicotine. Since the data on the effects of 5-HT receptor agonism on nicotine withdrawal signs are limited, we aimed to investigate whether 5-HT receptor agonism alleviated the behavioral and neurobiochemical (hippocampal neurogenesis) consequences of nicotine withdrawal in Sprague-Dawley rats. Our data indicate that withdrawal from nicotine self-administration induced locomotor hyperactivity, lengthened immobility time (the forced swim test), induced 'drug-seeking' behavior and deficits in cognition-like behavior (the novel object recognition task).

The effect of ageing and cerebral serotonin deficit on the activity of cytochrome P450 2D (CYP2D) in the brain and liver of male rats.

Brain cytochrome P450 (CYP) contributes to the local metabolism of endogenous substrates and drugs. The aim of present study was to ascertain whether the cytochrome P450 2D (CYP2D) activity changes with ageing and in cerebral serotonin deficit. Kinetics of 5-methoxytryptamine O-demethylation to serotonin was studied and the CYP2D activity was measured in brain and liver microsomes of Dark Agouti wild type (WT) rats (mature 3.

Valproic acid exposure impairs ultrasonic communication in infant, adolescent and adult rats.

Persistent deficits of social communication are a hallmark of autism spectrum disorders (ASD). Communication disabilities can be experimentally modeled using rodents' ultrasonic vocalizations (USVs). Although prenatal exposure to valproic acid (VPA) is one of the most widely used animal models of ASD, little is known about communication impairments in this model.

Distinct cognitive and discriminative stimulus effects of ketamine enantiomers in rats.

Although (S)-ketamine was approved for use in treatment-resistant depression in 2019, new preclinical findings suggest that (R)-ketamine might produce better efficacy and tolerability relative to (S)-ketamine. Here we evaluated the effects of (R)-, (S)-, and (R,S)-ketamine on executive functions as measured in the attentional set shifting task (ASST) and on their discriminative stimulus effects in rats. Earlier data demonstrated that cognitive flexibility is compromised by (R,S)-ketamine, but the effects of enantiomers in rats are unknown.

Effects of prenatal exposure to valproic acid or poly(I:C) on ultrasonic vocalizations in rat pups: The role of social cues.

Sociocommunicative deficits commonly observed in autism spectrum disorder (ASD) can be experimentally modeled using rodents' ultrasonic vocalizations (USVs). For example, USVs emitted by pups, separated from their mothers and nest, serve as a useful tool to identify autistic-like behaviors during the early period of development. Being sensitive to social context, these neonatal calls may help to reveal reduced social attachment or abnormal processing of social information.

Correction to: Desformylflustrabromine, a positive allosteric modulator of α4β2-containing nicotinic acetylcholine receptors, enhances cognition in rats.

The original article can be found online.

Desformylflustrabromine, a positive allosteric modulator of α4β2-containing nicotinic acetylcholine receptors, enhances cognition in rats.

Rationale: The α4β2 nicotinic acetylcholine receptors (α4β2-nAChRs) may represent useful targets for cognitive improvement. It has been recently proposed that a strategy based on positive allosteric modulation of α4β2-nAChRs reveals several advantages over the direct agonist approach. Nevertheless, the procognitive effects of α4β2-nAChR positive allosteric modulators (PAMs) have not been extensively characterized.

Social dysfunction in the neurodevelopmental model of schizophrenia in male and female rats: Behavioural and biochemical studies.

Social dysfunction is among the core symptoms of schizophrenia. The neuropeptides oxytocin (OXT) and vasopressin (VP) are involved in the regulation of social behaviour and social cognition. There are indications that both of these neurotransmitter systems are altered in schizophrenia.