Acute stress induces different changes on the expression of CB1 receptors in the hippocampus of two lines of male rats differing in their response to stressors.

The stress-induced alterations in cognitive processes and psychiatric disorders can be accelerated when acute stressors challenge the hippocampal functions. To address this issue, we used Western Blot (WB) and immunohistochemistry assays to investigate the impact of acute forced swimming (FS) on the expression of the CB1 cannabinoid receptors (CB1R) in the hippocampus (HC) of the male outbred Roman High- (RHA) and Low-Avoidance (RLA) rat lines, one of the most validated genetic models for the study of behavior related to fear/anxiety and stress-induced depression. The distinct responses to FS confirmed the different behavioral strategies displayed by the two phenotypes when exposed to stressors, with RLA and RHA rats displaying reactive vs.

Contrasting Effects of Oxytocin on MK801-Induced Social and Non-Social Behavior Impairment and Hyperactivity in a Genetic Rat Model of Schizophrenia-Linked Features.

Social withdrawal in rodents is a measure of asociality, an important negative symptom of schizophrenia. The Roman high- (RHA) and low-avoidance (RLA) rat strains have been reported to exhibit differential profiles in schizophrenia-relevant behavioral phenotypes. This investigation was focused on the study of social and non-social behavior of these two rat strains following acute administration of dizocilpine (MK801, an NMDA receptor antagonist), a pharmacological model of schizophrenia-like features used to produce asociality and hyperactivity.

Contribution of the Roman rat lines/strains to personality neuroscience: neurobehavioral modeling of internalizing/externalizing psychopathologies.

The Roman high-avoidance (RHA) and low-avoidance (RLA) rat lines/strains were established in Rome through bidirectional selection of Wistar rats for rapid (RHA) or extremely poor (RLA) acquisition of a two-way active avoidance task. Relative to RHAs, RLA rats exhibit enhanced threat sensitivity, anxiety, fear and vulnerability to stress, a passive coping style and increased sensitivity to frustration. Thus, RLA rats' phenotypic profile falls well within the "internalizing" behavior spectrum.

Schizophrenia-relevant social, attentional and cognitive traits in female RHA vs. RLA rats: Effects of neonatal handling.

The Roman high- (RHA) and low-avoidance (RLA) rats were bidirectionally selected and bred for, respectively, their rapid vs. extremely poor acquisition in the two-way active avoidance task. Consistent between-strain neurobehavioural differences have been found in anxiety- and stress-linked traits, as well as in schizophrenia-related phenotypes.

Atypical antipsychotics attenuate MK801-induced social withdrawal and hyperlocomotion in the RHA rat model of schizophrenia-relevant features.

Rationale: The administration of NMDA receptor (NMDAR) antagonists constitutes a widely used model that produce both positive (e.g., hyperactivity) and negative (e.

Effects of Tail Pinch on BDNF and trkB Expression in the Hippocampus of Roman Low- (RLA) and High-Avoidance (RHA) Rats.

In this article, we describe the effects of tail pinch (TP), a mild acute stressor, on the levels of brain-derived neurotrophic factor (BDNF) and its tyrosine kinase receptor B (trkB) proteins in the hippocampus (HC) of the outbred Roman High- (RHA) and Low-Avoidance (RLA) rats, one of the most validated genetic models for the study of fear/anxiety- and stress-related behaviors. Using Western blot (WB) and immunohistochemistry assays, we show for the first time that TP induces distinct changes in the levels of BDNF and trkB proteins in the dorsal (dHC) and ventral (vHC) HC of RHA and RLA rats. The WB assays showed that TP increases BDNF and trkB levels in the dHC of both lines but induces opposite changes in the vHC, decreasing BDNF levels in RHA rats and trkB levels in RLA rats.

A maturational shift in the frontal cortex synaptic transcriptional landscape underlies schizophrenia-relevant behavioural traits: A congenital rat model.

Disruption of brain development early in life may underlie the neurobiology behind schizophrenia. We have reported more immature synaptic spines in the frontal cortex (FC) of adult Roman High-Avoidance (RHA-I) rats, a behavioural model displaying schizophrenia-like traits. Here, we performed a whole transcriptome analysis in the FC of 4 months old male RHA-I (n=8) and its counterpart, the Roman Low-Avoidance (RLA-I) (n=8).

Acute Relaxation Response Induced by Tibetan Singing Bowl Sounds: A Randomized Controlled Trial.

The prevalence of anxiety has increased dramatically due to COVID-19, so effective preventive interventions are welcome. The main objective of our study was to compare the acute relaxation response (RR) induced by Tibetan singing bowl (TSB) sound-based treatment against progressive muscle relaxation (PMR) and a control waiting list group (CWL) in a single treatment session in an adult nonclinical anxious population. In this cross-sectional randomized control trial, 50 participants selected based on high state anxiety were randomly assigned to one of the experimental groups.

Neurobehavioral Profiles of Six Genetically-based Rat Models of Schizophrenia- related Symptoms.

Schizophrenia is a chronic and severe mental disorder with high heterogeneity in its symptoms clusters. The effectiveness of drug treatments for the disorder is far from satisfactory. It is widely accepted that research with valid animal models is essential if we aim at understanding its genetic/ neurobiological mechanisms and finding more effective treatments.

Acute Stress Induces Different Changes on the Expression of BDNF and trkB in the Mesocorticolimbic System of Two Lines of Rats Differing in Their Response to Stressors.

The present work was undertaken to investigate the effects of acute forced swimming (FS) on the levels of brain-derived neurotrophic factor (BDNF) and tyrosine kinase receptor B (trkB) proteins in: the ventral tegmental area (VTA); the nucleus accumbens (Acb) shell and core compartments; and the anterior cingulate (ACg), prelimbic (PL) and infralimbic (IL) territories of the prefrontal cortex of genetic models of vulnerability (RLA, Roman low-avoidance rats) and resistance (RHA, Roman high-avoidance rats) to stress-induced depression. We report for the first time that FS induced very rapid and distinct changes in the levels of BDNF and trkB proteins in different areas of the mesocorticolimbic system of RHA and RLA rats. Thus, (1) in the VTA and Acb core, FS elicited a significant increase of both BDNF- and trkB-LI in RHA but not RLA rats, whereas in the Acb shell no significant changes in BDNF- and trkB-LI across the line and treatment were observed; (2) in RLA rats, the basal levels of BDNF-LI in the IL/PL cortex and of trkB-LI in the ACg cortex were markedly lower than those of RHA rats; moreover, BDNF- and trkB-LI in the IL/PL and ACg cortex were increased by FS in RLA rats but decreased in their RHA counterparts.

Decreased activation of parvalbumin interneurons in the medial prefrontal cortex in intact inbred Roman rats with schizophrenia-like reduced sensorimotor gating.

Prepulse inhibition (PPI) allows assessing schizophrenia-like sensorimotor gating deficits in rodents. Previous studies indicate that PPI is modulated by the medial prefrontal cortex (mPFC), which is in agreement with our findings showing that PPI differences in the Roman rats are associated with divergences in mPFC activity. Here, we explore whether differences in PPI and mPFC activity in male Roman rats can be explained by (i) differences in the activation (c-Fos) of inhibitory neurons (parvalbumin (PV) interneurons); and/or (ii) reduced excitatory drive (PSD-95) to PV interneurons.

Different maturation patterns for sensorimotor gating and startle habituation deficits in male and female RHA vs RLA rats.

Neurodevelopmental anomalies are thought to play a crucial role in the emergence of schizophrenia. The Roman high-avoidance (RHA) rats exhibit impaired prepulse inhibition (PPI), as well as other behavioral and cognitive singularities related to schizophrenia syndromes compared to the Roman low-avoidance (RLA) rats. In the present study, we aimed at elucidating whether PPI deficits in the RHA rats take place during prepubescence, adolescence, or adulthood.

Prepulse inhibition deficits in inbred and outbred rats and between-strain differences in startle habituation do not depend on startle reactivity levels.

The acoustic startle response and prepulse inhibition (PPI) of startle are measures related to information processing, which is impaired in schizophrenia. Some studies have provided inconclusive patterns of association between both measures in rodents. We assessed the influence of baseline startle response on PPI in large samples of Roman high-(RHA) and low-avoidance (RLA) rat strains and in genetically heterogeneous stock (HS) rats.

Social preference in Roman rats: Age and sex variations relevance for modeling negative schizophrenia-like features.

Social withdrawal is one of the most relevant negative symptoms of schizophrenia. Animal models that mimic schizophrenia's symptoms, in general, and negative symptoms, in particular, are difficult to develop because of the high complexity of symptoms and neurochemical disturbances that schizophrenia patients display throughout their lives. In recent years we have shown that Roman High-Avoidance (RHA) rats exhibit some phenotypes that are thought to represent positive symptoms, cognitive/attentional symptoms, as well as some negative symptoms of the disease.

From Inhibition of GABA-A Receptor-Mediated Synaptic Transmission by Conventional Antidepressants to Negative Allosteric Modulators of Alpha5- GABA-A Receptors as Putative Fast-Acting Antidepressant Drugs: Closing the Circle?

The present perspective paper shortly and specifically addresses the issues of whether inhibition of GABA-A receptor-mediated synaptic transmission may be involved in antidepressantlike actions and the therapeutic effects of conventional antidepressant (AD) drugs, and whether the recent development of negative allosteric modulators (NAMs) of the alpha5-GABA-A receptor may constitute significant progress in our knowledge on the neurobiology and the treatment of depression.

Neurobehavioral and neurodevelopmental profiles of a heuristic genetic model of differential schizophrenia- and addiction-relevant features: The RHA vs. RLA rats.

The Roman High- (RHA) and Low-(RLA) avoidance rat lines/strains were generated through bidirectional selective breeding for rapid (RHA) vs. extremely poor (RLA) two-way active avoidance acquisition. Compared with RLAs and other rat strains/stocks, RHAs are characterized by increased impulsivity, deficits in social behavior, novelty-induced hyper-locomotion, impaired attentional/cognitive abilities, vulnerability to psychostimulant sensitization and drug addiction.

Oxytocin attenuates schizophrenia-like reduced sensorimotor gating in outbred and inbred rats in line with strain differences in CD38 gene expression.

Prepulse inhibition (PPI) of the startle response is a measure of sensorimotor gating that is impaired in many clinical conditions, including schizophrenia. The inbred Roman high-avoidance (RHA) rats, compared to their low-avoidance (RLA) counterparts, show distinct schizophrenia-like phenotypes, such as spontaneous deficits in PPI accompanied by decreased medial prefrontal cortex (mPFC) activity and volume. Schizophrenia-like deficits are usually attenuated by antipsychotic drugs, but these drugs often produce severe side effects.

Sex-specific effects of psychedelics on prepulse inhibition of startle in 129S6/SvEv mice.

Background: Prepulse inhibition (PPI) of startle is a sensorimotor gating phenomenon perturbed in a variety of neuropsychiatric conditions. Psychedelics disrupt PPI in rats and humans, but their effects and involvement of the serotonin 5-HT receptor (5-HTR) in mice remain unexplored.

Methods: We tested the effect of the psychedelic 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) (0.

Decreased social interaction in the RHA rat model of schizophrenia-relevant features: Modulation by neonatal handling.

The Roman-Low (RLA) and High-Avoidance (RHA) rat strains have been bidirectionally selected and bred, respectively, for extremely poor vs. rapid acquisition of the two-way active avoidance task. Over 50 years of selective breeding have led to two strains displaying many differential specific phenotypes.

Conflict between Threat Sensitivity and Sensation Seeking in the Adolescent Brain: Role of the Hippocampus, and Neurobehavioural Plasticity Induced by Pleasurable Early Enriched Experience.

Adolescence is characterized both by the exacerbation of the experience of anxiety, fear or threat, on one hand, and by increased reward seeking (reward sensitivity) and risk taking on the other hand. The rise of these apparently opposite processes, i.e.

Revisiting the role of anxiety in the initial acquisition of two-way active avoidance: pharmacological, behavioural and neuroanatomical convergence.

Two-way active avoidance (TWAA) acquisition constitutes a particular case of approach -avoidance conflict for laboratory rodents. The present article reviews behavioural, psychopharmacological and neuroanatomical evidence accumulated along more than fifty years that provides strong support to the contention that anxiety is critical in the transition from CS (conditioned stimulus)-induced freezing to escape/avoidance responses during the initial stages of TWAA acquisition. Thus, anxiolytic drugs of different types accelerate avoidance acquisition, anxiogenic drugs impair it, and avoidance during these initial acquisition stages is negatively associated with other typical measures of anxiety.