Behavioural Pharmacology最新文献

Cannabidiol (CBD) was first isolated in the 1940s and its drug structure was established in the 1960s. It has risen significantly in popularity since then and has been observed to reduce inflammation and anxiety in patients. CBD is easy to obtain and consume, therefore, its common use is rising and has spread to use in pets and children. Few studies have focused on the use of CBD as a solution to aggression. In our study, we tested if CBD is effective in reducing aggression in Siamese fighting fish ( Betta splendens ) induced by territorial interactions. Betta fish were exposed to controls (water or acetone) and CBD treatments ranging from low, medium, and high (2, 10, and 20 mg CBD/L, respectively), and their behaviors after the visual introduction of an intruder fish were recorded. CBD reduced the odds of aggressive behavior in treated fish. Seventy-five percent of all control fish exhibited aggressive behaviors, while only 17% of CBD-treated fish displayed aggression. Especially, the low CBD dose seemed effective at preventing aggressive behaviors but fish also appeared more lethargic than in any of the other treatments. However, when CBD-treated fish displayed aggressive behaviors, CBD did not appear to reduce the amount of time fish spent being aggressive compared to aggressive fish that did not receive any CBD treatment. While the long-term effects of CBD still have to be examined, our study indicates that CBD might be effective in reducing aggression in Betta fish and potentially other pets.

Research has indicated a strong link between exposure to aluminum (Al) and the development of Alzheimer's disease (AD). Given the rising use of Al nanoparticles, which are far more neurotoxic than Al, it is noteworthy to investigate the possible protective properties of natural substances. Curcumin, an important component of turmeric, has demonstrated neuroprotective effects in some animal studies. The main objective of this study was to examine the protective effects of curcumin on the memory deficit induced by subcutaneous aluminum oxide nanoparticles (Al-NP) administration in mice. Additionally, considering the roles of the hippocampal brain-derived neurotrophic factor (BDNF) and Akt pathway in AD pathology, their levels were evaluated. Adult male Swiss mice (SWR/J) were administered Al-NP (10 mg/kg/s.c.) with or without curcumin (2.5, or 25 mg/kg/P.O) for 10 days. Memory and anxiety-like behavior were assessed using passive avoidance and elevated plus maze tasks, respectively. Western blot analysis was employed to measure hippocampal BDNF and Akt proteins in the hippocampus. The findings revealed that Al-NP induced memory impairment in mice, whereas curcumin at 25 mg/kg prevented this memory deficit. Additionally, Al-NP significantly reduced the hippocampal BDNF and phosphorylated Akt levels, while curcumin increased BDNF and phosphorylated Akt to a nonsignificant level compared to the control group. These results not only suggest the neuroprotective properties of curcumin but also suggest a possible association between hippocampal BDNF and Akt signaling in the neuroprotective mechanism of this compound against Al-NP toxicity.

There are complex dysregulated pathways behind the pathogenesis of pain and inflammation. Because most of the present drugs have certain side effects or are not effective enough, providing novel multitargeting and potent therapeutic agents is of particular importance. This study investigates the antinociceptive effects of pelargonidin, an anthocyanin derived from various plants, through the modulation of the L-arginine/nitric oxide (NO)/cyclic GMP (cGMP)/ATP-sensitive potassium channel (K ATP ) signaling pathway. We also evaluated the anti-inflammatory role of pelargonidin passing through gamma-aminobutyric acid (GABA) and opioidergic receptors. Two experimental models were utilized. In the carrageenan model, 42 rats were divided into control, diclofenac, and three doses of pelargonidin (3, 6, and 9 mg/kg). In addition, two groups received pelargonidin 9 mg/kg + naloxone and pelargonidin 9 mg/kg + flumazenil. For the formalin model, 90 male mice were assigned to control, diclofenac, and three doses of pelargonidin, and 10 groups receiving L-arginine, S-nitroso- N -acetylpenicillamine (SNAP), N (gamma)-nitro-L-arginine methyl ester (L-NAME), glibenclamide, and sildenafil individually or alongside pelargonidin 9 mg/kg. Our results indicated that pelargonidin significantly decreased inflammation and pain in a dose-dependent manner. Notably, groups of pelargonidin 9 mg/kg + naloxone and pelargonidin 9 mg/kg + flumazenil diminished pelargonidin's anti-inflammatory effectiveness, underscoring the significant role of these receptors. Mechanistically, it was shown that the antinociceptive effects of pelargonidin were mediated by the NO signaling pathway. While L-NAME and glibenclamide reduced pelargonidin's antinociceptive efficacy, supplementation with sildenafil and SNAP enhanced the effect. This investigation demonstrated that pelargonidin possesses dose-dependent antinociceptive and anti-inflammatory actions through L-arginine/NO/cGMP/K ATP pathways, and opioidergic and GABA receptors, respectively.

Ketamine displays efficacious rapid-acting antidepressant (RAAD) activity in the rat chronic mild stress (CMS) model. It rapidly reverses anhedonia (CMS-induced sucrose consumption deficit) and attenuates working memory deficit (novel object recognition: NOR) following both systemic (intraperitoneal, i.p.) administration or local administration in the prefrontal cortex (PFC). However, the receptor mechanisms underlying these effects remain to be clarified and may involve activation of serotonin 5-HT 1A receptors, as previously found in experiments using the forced swim test. The present study explored the contribution of PFC 5-HT 1A receptors in ketamine's RAAD activity in the CMS model. Ketamine (10 mg/kg i.p.) reversed CMS-induced sucrose consumption and working memory (NOR test) deficits. Notably, unilateral PFC microinjections of a 5-HT 1A receptor antagonist, WAY-100635 (2 µg), prevented the antidepressant-like and pro-cognitive activity of systemic ketamine on sucrose consumption and working memory deficits. These data indicate that the RAAD activity of ketamine in the rat CMS model requires activation of PFC 5-HT 1A receptors. They also reinforce the notion that drugs that directly activate PFC 5-HT 1A receptors could constitute an alternative to ketamine as a promising strategy to achieve RAAD effects, with additional benefits against cognitive deficits in depressed patients, but without ketamine's troublesome side-effects and requirements for in-patient supervision.

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.