ATTENUATION OF STRESS INDUCED URINARY BIOCHEMICAL CHANGES AND SCOPOLAMINE-INDUCED MEMORY LOSS BY HYDROALCOHOLIC SEED EXTRACT OF CELASTRUS PANICULATUS WILLD. IN RAT MODEL

Ayurveda uses seeds of Celastrus paniculatus to treat various stress related disorders. In the present investigation, the hydroalcoholic seed extract of C. paniculatus was evaluated for anti-stress activity by forced swim stress model. Vanillylmandelic acid and ascorbic acid were selected as non-invasive biomarkers to assess the anti-stress activity. Nootropic activity in rats was evaluated by conditioned avoidance response using Cook’s pole climbing apparatus, the antioxidant potential was determined based on the ability of the extract to scavenge hydroxyl radicals. Pretreatment with the extract significantly (p < 0.05) inhibited the stress induced urinary biochemical levels. The cognition was observed to be dose dependent. The extract also produced significant dose dependent inhibition of hydroxyl radicals. The present study provides scientific support for the anti-stress, antioxidant and nootropic activities of hydroalcoholic seed extract of C. paniculatus and substantiates the traditional claims for the usage of C. paniculatus willd. in stress induced disorders.

Disruption of Long-Term Depression Potentiates Latent Inhibition: Key Role for Central Nucleus of the Amygdala

Background Latent inhibition (LI) reflects an adaptive form of learning impaired in certain forms of mental illness. Glutamate receptor activity is linked to LI, but the potential role of synaptic plasticity remains unspecified. Methods Accordingly, the present study examined the possible role of long-term depression (LTD) in LI induced by prior exposure of rats to an auditory stimulus used subsequently as a conditional stimulus to signal a pending footshock. We employed 2 mechanistically distinct LTD inhibitors, the Tat-GluA23Y peptide that blocks endocytosis of the GluA2-containing glutamate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor, or the selective glutamate n-methyl-d-aspartate receptor 2B antagonist, Ro25-6981, administered prior to the acquisition of 2-way conditioned avoidance with or without tone pre-exposure. Results Systemic LTD blockade with the Tat-GluA23Y peptide strengthened the LI effect by further impairing acquisition of conditioned avoidance in conditional stimulus-preexposed rats compared with normal conditioning in non-preexposed controls. Systemic Ro25-6981 had no significant effects. Brain region–specific microinjections of the Tat-GluA23Y peptide into the nucleus accumbens, medial prefrontal cortex, or central or basolateral amygdala demonstrated that disruption of glutamate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor endocytosis in the central amygdala also potentiated the LI effect. Conclusions These data revealed a previously unknown role for central amygdala LTD in LI as a key mediator of cognitive flexibility required to respond to previously irrelevant stimuli that acquire significance through reinforcement. The findings may have relevance both for our mechanistic understanding of LI and its alteration in disease states such as schizophrenia, while further elucidating the role of LTD in learning and memory.

The Effect of Social Anxiety on the Acquisition and Extinction of Low-Cost Avoidance

Excessive avoidance and safety behaviours are a hallmark feature of social anxiety disorder. However, the conditioning and extinction of avoidance behaviour in social anxiety is understudied. Here, we examined the effect of individual differences in social anxiety on low-cost operant avoidance conditioning and extinction in 80 female participants. We employed an avoidance conditioning and extinction paradigm and measured skin conductance response, threat expectancy ratings and avoidance behaviour throughout the task. Findings demonstrated that elevated levels of social anxiety predicted the generalisation of conditioned avoidance responses across to safety cues during avoidance conditioning. When the opportunity to avoid was returned after extinction learning, elevated social anxiety was associated with increased avoidance behaviour to both threat and safety cues. The results suggest that compromised extinction of avoidance behaviour is a characteristic of social anxiety and supports the strategy of minimising avoidance and safety behaviours during exposure therapy for the treatment of social anxiety disorder. Future research should utilise the avoidance conditioning and extinction paradigm as a laboratory model for clinical research to investigate how, and under what circumstances, the extinction of avoidance and safety behaviours can be improved for individuals high in social anxiety.

Decomposing conditioned avoidance performance with computational models

Avoidance towards innocuous stimuli is a key characteristic across anxiety-related disorders and chronic pain. Insights into the relevant learning processes of avoidance are often gained via laboratory procedures, where individuals learn to avoid stimuli or movements that have been previously associated with an aversive stimulus. Typically, statistical analyses of data gathered with conditioned avoidance procedures include frequency data, for example, the number of times a participant has avoided an aversive stimulus. Here, we argue that further insights into the underlying processes of avoidance behavior could be unraveled using computational models of behavior. We then demonstrate how computational models could be used by reanalysing a previously published avoidance data set and interpreting the key findings. We conclude our article by listing some challenges in the direct application of computational modeling to avoidance data sets.

A novel allosteric modulator of the cannabinoid CB1 receptor ameliorates hyperdopaminergia endophenotypes in rodent models

The endocannabinoid system (eCBs) encompasses the endocannabinoids, their synthetic and degradative enzymes, and cannabinoid (CB) receptors. The eCBs mediates inhibition of neurotransmitter release and acts as a major homeostatic system. Many aspects of the eCBs are altered in a number of psychiatric disorders including schizophrenia, which is characterized by dysregulation of dopaminergic signaling. The GluN1-Knockdown (GluN1KD) and Dopamine Transporter Knockout (DATKO) mice are models of hyperdopaminergia, which display abnormal psychosis-related behaviors, including hyperlocomotion and changes in pre-pulse inhibition (PPI). Here, we investigate the ability of a novel CB1 receptor (CB1R) allosteric modulator, ABM300, to ameliorate these dysregulated behaviors. ABM300 was characterized in vitro (receptor binding, β-arrestin2 recruitment, ERK1/2 phosphorylation, cAMP inhibition) and in vivo (anxiety-like behaviors, cannabimimetic effects, novel environment exploratory behavior, pre-pulse inhibition, conditioned avoidance response) to assess the effects of the compound in dysregulated behaviors within the transgenic models. In vitro, ABM300 increased CB1R agonist binding but acted as an inhibitor of CB1R agonist induced signaling, including β-arrestin2 translocation, ERK phosphorylation and cAMP inhibition. In vivo, ABM300 did not elicit anxiogenic-like or cannabimimetic effects, but it decreased novelty-induced hyperactivity, exaggerated stereotypy, and vertical exploration in both transgenic models of hyperdopaminergia, as well as normalizing PPI in DATKO mice. The data demonstrate for the first time that a CB1R allosteric modulator ameliorates the behavioral deficits in two models of increased dopamine, warranting further investigation as a potential therapeutic target in psychiatry.

Assessment of the influence of cilostazol on learning-memory and motor co-ordination by rodent models

Dementia is a set of symptoms that include worsening of the routine of cognitive tasks, learning, reproducibility, and gait disturbances beyond typical aging. Activated c AMP can produce anti-apoptosis activity, neuroprotective activity, motor improvement, and cognitive enhancement activity. Cilostazol can increase c AMP levels, so this study aimed to evaluate the influence of cilostazol on learning-memory and motor coordination by rodent models. The rats were divided into 5 and 6 groups with 6 rats in each to test the hypothesis respectively. Before MES seizure induction the rats were trained for conditioned avoidance response for 14 days and the best one was selected for assessment. The performance of intervention treated groups to determine the memory retention effect was measured by applying a fixed number of shocks. The intervention treated groups were tested for motor coordination performance by rotarod test (4-45 RPM accelerating speed for 5 min) after 30 and 60 min. The latency time of each rat falls off from the rod for the first time was noted. The results were presented as Mean ± SD, tested by ordinary two way ANOVA followed by Tukey's multiple comparisons test. Cilostazol 100 mg/kg p.o demonstrated a significant memory enhancement activity in the conditioned avoidance response technique. Cilostazol 20mg/kg i.p alone and along with diazepam 2 mg/kg demonstrated a significant motor coordination performance in both sessions. The present study concludes that cilostazol has improved the learning & memory and motor coordination performances.