Behavioural Pharmacology最新文献

Social safety learning refers to the process by which animals indirectly learn about the safety of novel stimuli. This process is critical when rodents decide what to eat since they lack the capacity to vomit, reducing their ability to expel ingested toxins. Consequently, rodents display neophobia when encountering novel food, but are more likely to eat the food when a conspecific signals its safety. This natural behavior is modeled using the social transmission of food preference (STFP) paradigm. Based on behavioral and neural insights into STFP, I argue in the current work that its acquisition may involve cognitive processes that extend beyond social safety learning. Specifically, I argue that STFP acquisition may parallel functional aspects of human epistemic trust. Epistemic trust refers to trust in communicated knowledge, enabling humans to learn from, adapt to, and respond to their (social) environment. This perspective could position the STFP paradigm as a valuable tool to investigate the neurobiology of cognitive processes that may be relevant to human epistemic trust. Given the importance of epistemic trust in therapeutic settings, understanding its neurobiology may have direct clinical implications.

Mood disorders are a prevalent global health concern with natural health products, including herbal supplements, an increasingly popular choice as an alternative or complementary therapy. Despite their widespread use, few studies have tested the clinical efficacy of natural health products or explored their underlying mechanisms in animal models. Modification of affective biases has been linked to mood in humans and animal models and may provide insights into potential antidepressant effects. In this study, we used a translational rodent model of affective bias modification to investigate the effects of five commonly used supplements: Hypericum perforatum , that is, St. John's Wort (SJW), Mucuna pruriens , Rhodiola rosea root extract, Valerian root extract and 5-hydroxytryptophan. Exercise is also thought to improve mood disorders, but clinical studies reveal mixed results therefore we also tested the effect of involuntary exercise on affective biases. In separate experiments, male Lister Hooded rats were acutely treated with SJW, Mucuna pruriens , Rhodiola rosea root extract, Valerian root extract and 5-hydroxytryptophan, or underwent an involuntary exercise manipulation. Our results showed a significant positive affective bias following treatment with SJW, whilst the involuntary exercise induced a negative affective bias in rats. No effects were found following the other acute treatments. These data suggest SJW has similar effects in terms of affective bias modification as conventional antidepressants. The negative affective bias observed with involuntary exercise suggests the animals experience a negative affective state and suggests exercise-based therapy may be less effective if the patient perceives this as involuntary.

Early animal models of depression focused on developing methods that could predict treatment efficacy and were validated based on pharmacological responses to known antidepressants. As our understanding of major depressive disorder (MDD) and the pharmacology of antidepressants progressed, so did the need for better animal models. This need was met with the development of new disease models, such as the chronic mild stress model, and behavioural readouts such as the sucrose preference test, which more closely aligned with risk factors and symptoms seen in patients. These approaches have supported huge advances in the understanding of how stress affects the brain and impacts on reward-related behaviours. However, there remain significant challenges when trying to model complex psychiatric symptoms and disorders in non-human animals. In this perspective article, a brief history of animal models of depression and associated readouts is discussed with specific reference to the important contributions from Paul Willner. The main discussion then focuses on translational validity and approaches that may support delivering this objective. This is illustrated with the example of the affective bias test and reward learning assays, which have been developed to recapitulate in animals the neuropsychological impairments observed in MDD and modulation by antidepressants.

Despite major advances in neuroscience, there has been limited progress in improving pharmacological treatment for neuropsychiatric disorders. Neuropsychiatric disorders are heterogeneous with variance in symptoms within disorders and partial overlap in symptoms between disorders, leading to symptoms that remain untreated. To improve treatment outcomes, neuroscience has shifted to examining the neurobiological mechanisms underlying individual components, or dysfunctions, across disorders. Anhedonia, a decreased capacity to experience pleasure from positive stimuli or rewards, is a prominent symptom associated with poor functional outcome across neuropsychiatric disorders. This article reflects on Professor Paul Willner's contributions to the field of behavioural neuroscience, specifically his promotion of validity in animal models of neuropsychiatric disorders. Research can build upon Willner's scholarship by continuing to refine and explore the validity of animal models as our understanding of neuropsychiatric disorders improves. To exemplify this, we discuss current understanding of the neurobiological basis and clinical presentation of the two domains of anhedonia: anticipation and consumption. We argue for the examination of anticipatory anhedonia and consummatory anhedonia within a single paradigm to improve understanding of these domains, aligning animal models to the clinical reality in humans.

Recent evidence suggests that cannabis can impair simple auditory processes, and these alterations might be due to cannabinoid agonism. The effect of cannabinoid agonism on relatively complex processes such as auditory discrimination is unknown. The goal of this study was to examine the impact of WIN 55,212-2, a CB 1 receptor and CB 2 receptor agonism, on auditory discrimination using a go/no-go task. Twenty-two male and female Sprague-Dawley rats were initially trained to lever-press for sucrose to either a pure tone or white noise cue in a go/no-go paradigm, where rats were reinforced for lever-pressing during one cue and punished for lever-pressing during the other auditory cue. After criterion performance was met, rats were then injected with WIN 55,212-2 at 1.2 mg/kg, 3 mg/kg, or a corresponding vehicle (saline) and were tested on auditory discrimination. On day 3, active lever-pressing was higher in both the low- and high-dose WIN groups compared with the saline group. Overall lever-pressing decreased over time in the high-dose WIN 55,212-2 group. There were no effects of the drug on discrimination or errors, suggesting that cannabinoid agonism did not negatively affect auditory discrimination. This is the first study to examine the impact of cannabinoids on the discrimination of tones, finding that, contrary to previous research, the low and high doses of WIN 55,212-2 did not adversely impact auditory-linked behaviors.

Maternal separation as an early life stress can lead to long-lasting deleterious effects on cognitive and behavioral functions, and the mood state. On the other hand, Psilocybe cubensis (as one of the most well-known magic mushrooms) may be beneficial in the improvement or the treatment of neuropsychiatric disorders. In the present study, we aimed to investigate the effect of P. cubensis extract (PCE) on depressive-like and anxiety-like behaviors, and locomotor activity in mice exposed to early maternal separation. Also, we assessed the expression and methylation level of Slc6a4 and Nr3c1 in the hippocampus. Maternal separation was done in postnatal days (PNDs) 2-18. PCE was intraperitoneally injected at the dose of 20 mg/kg at PND 60, and our tests were done at days 1, 3, and 10, of administration. The results showed that maternal separation significantly induced depressive-like behavior in the forced swim test and anxiety-like behavior in the open field test (OFT). Also, maternal separation decreased locomotor activity in the OFT. In addition, maternal separation decreased the expression and increased the methylation level of both Slc6a4 and Nr3c1 in the hippocampus. However, PCE significantly reversed all these effects. In conclusion, it seems that P. cubensis affects serotonergic signaling via altering Slc6a4 expression and methylation level in the hippocampus of mice. The effect of P. cubensis on Nr3c1 expression and methylation level may also lead to alter the function of the hypothalamus-pituitary-adrenal axis and the stress response in mice exposed to maternal separation.

Memory retrieval involves recalling previously consolidated information, while memory extinction refers to the gradual weakening of such memories after recall. Stress and glucocorticoids influence the retrieval and extinction of memory. This study employed a passive avoidance task to examine the impact of acute mild stress and equivalent doses of exogenous corticosterone on fear memory retrieval and extinction in male mice. Subsequently, we investigated the potential therapeutic effects of Ginkgo biloba extract, EGb 761, on memory impairments induced by stress and corticosterone. Corticosterone was administered systemically 30 min before memory reactivation to model glucocorticoid activity during retrieval. Mild acute stress, like the stress levels typically experienced before an exam, was induced through 20-min restraint immediately before reactivation in separate groups. EGb 761 was injected 30 min before corticosterone or stress exposure. Results demonstrated that both corticosterone and acute stress impaired context-specific fear memory retrieval and enhanced subsequent extinction. Pretreatment with EGb 761 inhibited these impairing effects of acute stress and corticosterone on avoidance memory retrieval and extinction. Our findings suggest that the glucocorticoid system and acute stress markedly influence avoidance memory retrieval and extinction. Ginkgo biloba may possess therapeutic and memory-enhancing effects, particularly in stressful situations.