Using Appetitive Motivation to Train Mice for Spatial Learning in the Barnes Maze.

The Barnes maze, a well-known spatial-learning paradigm, is based on the innate fear of rodents of large open spaces and their drive to hide. However, additional aversive stimuli (strong light and threatening sounds) are often necessary to provoke the hiding response while rendering the method cumbersome and more stressful. Our objective was to establish a Barnes maze-learning paradigm in mice using palatable food as a reward.

Age-related decline of various cognitive functions in well-experienced male rats treated with the putative anti-aging compound (2R)-1-(1-benzofuran-2-yl)-N-propylpentane-2-amine ((-)BPAP).

Aging-associated cognitive disorders lack proper medication. To meet this need translation-wise, modification of the animal models is also required. In the present study, effect of the putative anti-aging compound (2R)-1-(1-benzofuran-2-yl)-N-propylpentane-2-amine ((-)BPAP, a deprenyl derivative) on age-related cognitive decline was investigated in experienced, aged Long-Evans rats.

Corrigendum: Intracerebroventricularly Injected Streptozotocin Exerts Subtle Effects on the Cognitive Performance of Long-Evans Rats.

[This corrects the article DOI: 10.3389/fphar.2021.

Performance of the intracerebroventricularly injected streptozotocin Alzheimer's disease model in a translationally relevant, aged and experienced rat population.

The intracerebroventricularly (icv) injected streptozotocin (STZ) induced brain state is a widely used model of sporadic Alzheimer-disease (AD). However, data have been generated in young, naive albino rats. We postulate that the translationally most relevant animal population of an AD model should be that of aged rats with substantial learning history.

Introduction of a pharmacological neurovascular uncoupling model in rats based on results of mice.

Our aim was to establish a pharmacologically induced neurovascular uncoupling (NVU) method in rats as a model of human cognitive decline. Pharmacologically induced NVU with subsequent neurological and cognitive defects was described in mice, but not in rats so far. We used 32 male Hannover Wistar rats.

Lack of general learning ability factor in a rat test battery measuring a wide spectrum of cognitive domains.

: In the framework of a larger project aiming to test putative cognitive enhancer drugs in a system with improved translational validity, we established a rodent test battery, where different, clinically relevant cognitive domains were investigated in the same animal population. The aim of the current study was to check whether performances in the different tasks representing different cognitive functions are assay-specific or may originate in an underlying general learning ability factor. : In the experiments 36 Long-Evans and 36 Lister Hooded rats were used.

Cognitive profiling and proteomic analysis of the modafinil analogue S-CE-123 in experienced aged rats.

The lack of novel cognitive enhancer drugs in the clinic highlights the prediction problems of animal assays. The objective of the current study was to test a putative cognitive enhancer in a rodent cognitive test system with improved translational validity and clinical predictivity. Cognitive profiling was complemented with post mortem proteomic analysis.

Intracerebroventricularly Injected Streptozotocin Exerts Subtle Effects on the Cognitive Performance of Long-Evans Rats.

Intracerebroventricularly injected streptozotocin (STZ)-induced learning impairment has been an increasingly used rat model of Alzheimer disease. The evoked pathological changes involve many symptoms of the human disease (cognitive decline, increase in β-amyloid and phospho-tau level, amyloid plaque-like deposits). However, the model has predominantly been used with Wistar rats in the literature.

Procognitive profiling of a serotonin 5-HT receptor antagonist in a complex model system in rats: A novel translational approach for clinical prediction.

Introduction: The serial clinical failures of novel cognitive enhancer candidates point out the lack of predictive power in the preceding animal experimentation. For a more predictive profiling of putative procognitive drugs in rodents, we recently elaborated a methodical approach which consists of three fundamental steps: 1. teaching various learning tasks representing different cognitive domains to the same cohort of animals with the aim to create a population with 'widespread knowledge'.

How can preclinical cognitive research further neuropsychiatric drug discovery? Chances and challenges.

Introduction: Disorders of the brain pose the biggest health challenge of this century with new and highly efficacious medications urgently needed. This article discusses the challenges of meeting this increasing demand by neuropsychiatric drug discovery.

Areas Covered: The current psychopharmacological armamentarium relies on targets discovered several decades ago.

Translational Difficulties in Querying Rats on "Orientation".

The aim of this study was to translate the "orientation" query of the ADAS-Cog inventory to rats and to investigate whether they can determine which time of the day they are. For this purpose, we established a modified Morris water-maze navigation task where the escape platform was placed onto various locations at different times of the day: "morning", "noon" and "evening". In each of these sessions rats swam a "query" trial and a "confirmatory" trial, 30 min apart.

Preclinical pharmacodynamic and pharmacokinetic characterization of the major metabolites of cariprazine.

Introduction: Cariprazine, a dopamine D-preferring D/D receptor partial agonist and serotonin 5-HT receptor partial agonist, has two major human metabolites, desmethyl-cariprazine (DCAR) and didesmethyl-cariprazine (DDCAR). The metabolite pharmacology was profiled to understand the contribution to cariprazine efficacy.

Methods: In vitro receptor binding and functional assays, electrophysiology, animal models, microdialysis, and kinetic-metabolism approaches were used to characterize the pharmacology of DCAR and DDCAR.

Following of aging process in a new motor skill learning model, "pot jumping" in rats.

Impairment of procedural memory is a frequent and severe symptom in many neurological and psychiatric diseases as well as during aging. Our aim was to establish an assay in rats in which procedural learning and changes in performance can be studied on the long term. The work was done in the frame of a larger project aiming to establish a complex cognitive animal test battery of high translational value.

Establishment of a rodent cooperation assay as a model of social cognition.

Introduction: Impaired cooperative skills form a characteristic symptom in autism, which lacks adequate treatment. The objective of this study was to establish a rat cooperation assay which fits the feasibility and capacity requirements of drug development.

Methods: Long-Evans and Lister Hooded rats were trained in pairs to simultaneously perform nose-pokes (within 1 s) for reward in a Skinner box equipped with two nose-poke modules.

Selegiline reduces adiposity induced by high-fat, high-sucrose diet in male rats.

Background And Purpose: Incidence and severity of obesity are increasing worldwide, however, efficient and safe pharmacological treatments are not yet available. Certain MAO inhibitors reduce body weight, although their effects on metabolic parameters have not been investigated. Here, we have assessed effects of a widely used, selective MAO-B inhibitor, selegiline, on metabolic parameters in a rat model of diet-induced obesity.

Effects of cariprazine on extracellular levels of glutamate, GABA, dopamine, noradrenaline and serotonin in the medial prefrontal cortex in the rat phencyclidine model of schizophrenia studied by microdialysis and simultaneous recordings of locomotor activity.

Rationale: Aberrant glutamatergic, dopaminergic, and GABAergic neurotransmission has been implicated in schizophrenia. Cariprazine reverses the behavioral effects observed in the rat phencyclidine (PCP)-induced model of schizophrenia; however, little is known about its in vivo neurochemistry.

Objectives: The study aims to compare the effects of cariprazine and aripiprazole on PCP-induced changes in the extracellular levels of glutamate, dopamine, serotonin, noradrenaline, and GABA in the rat medial prefrontal cortex (mPFC), and on locomotor activation.

Correction to: The Effects of Cariprazine and Aripiprazole on PCP-Induced Deficits on Attention Assessed in the 5-Choice Serial Reaction Time Task.

The article The Effects of Cariprazine and Aripiprazole on PCP-Induced Deficits on Attention Assessed in the 5-Choice Serial Reaction Time Task, written by Samuel A. Barnes, Jared W. Young, Athina Markou, Nika Adham, István Gyertyán, Béla Kiss, was originally published electronically.

The Effects of Cariprazine and Aripiprazole on PCP-Induced Deficits on Attention Assessed in the 5-Choice Serial Reaction Time Task.

Rationale: Attentional processing deficits are a core feature of schizophrenia, likely contributing to the persistent functional and occupational disability observed in patients with schizophrenia. The pathophysiology of schizophrenia is hypothesized to involve dysregulation of NMDA receptor-mediated glutamate transmission, contributing to disruptions in normal dopamine transmission. Preclinical investigations often use NMDA receptor antagonists, such as phencyclidine (PCP), to induce cognitive disruptions relevant to schizophrenia.

Effects on Sperms' Quality of Selegiline in Aged Rats.

Background: Selegiline is used to treat Parkinsonian patients. Other indications of its use have recently been discovered.

Objective: Scouting special and beneficial side effects of selegiline treatment.

Classification and reporting of severity experienced by animals used in scientific procedures: FELASA/ECLAM/ESLAV Working Group report.

Directive 2010/63/EU introduced requirements for the classification of the severity of procedures to be applied during the project authorisation process to use animals in scientific procedures and also to report actual severity experienced by each animal used in such procedures. These requirements offer opportunities during the design, conduct and reporting of procedures to consider the adverse effects of procedures and how these can be reduced to minimize the welfare consequences for the animals. Better recording and reporting of adverse effects should also help in highlighting priorities for refinement of future similar procedures and benchmarking good practice.

Pharmacological comparison of traditional and non-traditional cannabinoid receptor 1 blockers in rodent models in vivo.

Cannabinoid receptor 1 (CB1R) antagonists have been proven to be effective anti-obesity drugs; however, psychiatric side effects have halted their pharmaceutical development worldwide. Despite the emergence of next generation CB1R blockers, a preclinical head to head comparison of the anti-obesity and psychiatric side effect profiles of the key compounds has not been performed. Here, we compared classical CB1R antagonists (rimonabant, taranabant, otenabant, ibipinabant, and surinabant) and non-traditional CB1R blockers (the partial agonist O-1269, the neutral antagonists VCHSR and LH-21 and the peripherally acting inverse agonist JD-5037) using an in vivo screening cascade.

Cariprazine Exhibits Anxiolytic and Dopamine D3 Receptor-Dependent Antidepressant Effects in the Chronic Stress Model.

Background: Cariprazine, a D3-preferring dopamine D2/D3 receptor partial agonist, is a new antipsychotic drug recently approved in the United States for the treatment of schizophrenia and bipolar mania. We recently demonstrated that cariprazine also has significant antianhedonic-like effects in rats subjected to chronic stress; however, the exact mechanism of action for cariprazine's antidepressant-like properties is not known. Thus, in this study we examined whether the effects of cariprazine are mediated by dopamine D3 receptors.

Long-term effects of aripiprazole exposure on monoaminergic and glutamatergic receptor subtypes: comparison with cariprazine.

Objective: This study examined the chronic effects of aripiprazole and cariprazine on serotonin (5-HT1A and 5-HT2A) and glutamate (NMDA and AMPA) receptor subtypes. In addition, the effects of aripiprazole on D2 and D3 receptors were tested and compared with previously reported cariprazine data.

Methods: Rats received vehicle, aripiprazole (2, 5, or 15 mg/kg), or cariprazine (0.

Cognitive 'Omics': Pattern-Based Validation of Potential Drug Targets.

Despite the abundance of cognitive enhancer mechanisms identified in basic research, drugs approved for cognitive disorders are scarce and of limited efficacy. Although the so-called 'gold-standard' animal assays are well suited to the study of fundamental learning processes, they fail to predict clinical efficacy against complex and robust cognitive defects. Preclinical validation of potential drug targets requires new approaches with higher translational value.

The influence of 5-HT(2A) activity on a 5-HT(2C) specific in vivo assay used for early identification of multiple acting SERT and 5-HT(2C) receptor ligands.

As a result of our exploratory programme aimed at elaborating dually acting compounds towards the serotonin (5-HT) transporter (SERT) and the 5-HT2C receptor a novel series of 3-amino-1-phenylpropoxy substituted diphenylureas was identified. From that collection two promising compounds (2 and 3) exhibiting highest 5-HT2C receptor affinity strongly inhibited the 5-HT2C receptor agonist 1-(3-chlorophenyl)piperazine (mCPP) induced hypomotility in mice. In further pursuance of that objective (2-aminoethyl)(benzyl)sulfamoyl diphenylureas and diphenylpiperazines have also been elaborated.