Paracetamol can induce hypothermia in humans and rodents. The study’s aim is to review the mechanisms of paracetamol-induced hypothermia in rodents or the results issued from in vitro studies on the same species’ tissues (in doses that do not produce hepatic impairment) using the latest developments published in scientific journals over the last 15 years. Available human studies are also analysed. An extensive search in PubMed databases exploring the hypothermic response to paracetamol was conducted. 4669 articles about paracetamol’s effects on body temperature in mice or rats were found. After applying additional filters, 20 articles were selected for review, with 9 of them presented in tabular forms. The analysis of these articles found that the hypothermic effect of paracetamol is due to the inhibition of a cyclooxygenase-1 variant, is potentiated by endothelin receptor antagonists, and can be mediated through GABA_A receptors and possibly through transient receptor potential cation channel subfamily A member 1 via N-acetyl-p-benzoquinone imine in the central nervous system. Human studies confirm the in vivo and in vitro experiments in rodents regarding the presence of a hypothermic effect after high, non-toxic doses of paracetamol. Further research is required to understand the mechanisms behind paracetamol’s hypothermic effect in humans.

The current study evaluated the anticonvulsant properties of ethanolic extracts from Morus alba, Angelica archangelica, Passiflora incarnata, and Valeriana officinalis using integrated phytochemical, in vivo, biochemical, and computational approaches. Phytochemical analysis by UHPLC-HRMS/MS revealed the presence of various bioactive compounds, notably flavonoids such as isorhamnetin, quercetin, and kaempferol. In an electroshock-induced seizure model, Morus alba extract (MAE, 100 mg/kg) demonstrated significant anticonvulsant effects, reducing both seizure duration and incidence, likely mediated by flavonoid interactions with GABA-A and 5-HT3A receptors, as suggested by target prediction and molecular docking analyses. The extracts of Angelica archangelica (AAE, 100 mg/kg) and Passiflora incarnata (PIE, 50 mg/kg) exhibited moderate, non-significant anticonvulsant activities. At the same time, Valeriana officinalis (VOE, 50 mg/kg) displayed considerable antioxidant and anti-inflammatory properties but limited seizure protection. All extracts significantly reduced brain inflammation markers (TNF-α) and enhanced antioxidant defenses, as indicated by total thiols. Molecular docking further supported the interaction of key phytochemicals, including naringenin and chlorogenic acid, with human and mouse 5-HT3A receptors. Overall, Morus alba extract exhibited promising therapeutic potential for epilepsy management, warranting further investigation into chronic seizure models and optimized dosing strategies.

Diabetic neuropathy (DN) is one of the most prevalent complications of diabetes mellitus, affecting a substantial proportion of patients and contributing to progressive sensorimotor dysfunction. Despite its clinical significance, available treatments are often insufficient and associated with undesirable effects. This study aims to evaluate the potential of Morus alba (MA), Angelica archangelica (AA), Valeriana officinalis (VO), and Passiflora incarnata (PI) extracts in ameliorating nociceptive alterations and inflammatory markers in the alloxan-induced diabetic rat model. Male Wistar rats with alloxan-induced DN received oral administration of the plant extracts (200 mg/kg/day) or gabapentin (100 mg/kg/day) for 15 days, the dosage regimen being established based on prior efficacy data in preclinical neuropathy models. Behavioral assessments of thermal and mechanical hypersensitivity were conducted using hot plate, tail withdrawal, von Frey, and Randall–Sellito tests. Tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels were quantified in brain and liver homogenates to evaluate neuro-inflammatory responses. All plant extracts produced significant improvements in nociceptive thresholds compared to diabetic control, with the most marked effects observed for MA extract. Pro-inflammatory cytokine levels were significantly reduced in all treatment groups, with MA and AA extracts inducing the most significant reductions in TNF-α and IL-6 concentrations. Computational target prediction and molecular docking analyses revealed that key phytochemicals from the plant extracts may exert antihyperalgesic effects through multi-target modulation, notably via interactions with AAK1, a kinase involved in neuropathic pain signaling. The investigated plant extracts displayed significant antihyperalgesic and anti-inflammatory activities in a rat model of DN. Among them, MA extract revealed the most consistent therapeutic profile, supporting its potential role as a strategy for managing DN.

Background/Objectives: Neuroinflammation is increasingly recognized as an important contributor to Alzheimer-like cognitive impairment. Lipopolysaccharide (LPS) is commonly used in experimental models to trigger systemic immune activation and behavioral alterations associated with neuroinflammation. This study aimed to validate a subacute LPS-induced model of recall-phase impairment and to compare the effects of donepezil and tacrine on recall-related exploratory behavior in rats. Methods: Male Wistar rats were tested in a two-trial Y-maze paradigm consisting of an acquisition trial followed by a recall trial 24 h later. In the validation experiment, rats received saline or LPS 1 mg/kg intraperitoneally for four consecutive days. In the intervention experiment, rats received saline, LPS, or LPS combined with donepezil 1 or 3 mg/kg or tacrine 3 or 5 mg/kg. The primary recall-phase outcome was the unknown/known arm time ratio (U/K time ratio). Additional outcomes included arm times, arm entries, U/K entry ratios, discrimination indices, and mean time per entry. Results: Repeated LPS administration significantly reduced the U/K time ratio, decreased time- and entry-based discrimination indices, reduced time spent in the unknown arm, and decreased unknown-arm entries, without significantly altering acquisition-phase behavior, total entries, or mean time per entry. In the intervention experiment, donepezil 1 mg/kg and tacrine 5 mg/kg significantly increased the U/K time ratio compared with LPS. Discrimination indices and entry-based measures further supported a treatment-related shift toward novelty-directed exploration, while total arm entries and mean time per entry were not significantly changed. Conclusions: Subacute LPS administration produced a measurable recall-phase exploratory impairment in the Y-maze. Donepezil and tacrine attenuated several components of this impairment, with partially distinct dose-related behavioral profiles.

Venlafaxine, a serotonin–norepinephrine reuptake inhibitor, shows analgesic effects in rodents, but its efficacy and pharmacological profile in acute stimulus-evoked nociception may depend on the nociceptive test used and the pharmacological context. The aim of this review was to identify the receptors implicated in venlafaxine antinociceptive effects and to examine which molecular processes most consistently explain its acute antinociceptive profile. We reviewed in vivo rodent studies testing venlafaxine in acute nociceptive assays (writhing, tail-flick, hot-plate, and other eligible acute tests) as monotherapy or associated with other pharmacologically active substances. PubMed/MEDLINE and Web of Science were searched from 1993 to 5 January 2026, and reference lists were also screened. Outcomes were synthesized and stratified by type of nociceptive test and interaction class. Fourteen studies were identified as relevant to the scope of this review. Venlafaxine produced dose-dependent antinociception across tests, reducing writhing and increasing thermal withdrawal latency. Central administration generally yielded effects at lower absolute doses than systemic routes. Interaction studies most consistently supported modulation of opioid receptors (e.g., leftward opioid dose–response shifts and attenuation of morphine tolerance in repeated-exposure designs), with convergent evidence implicating opioid and α₂-adrenergic mechanisms and context-dependent serotonergic contributions. Additional pathways were variably implicated, including nitric oxide—cyclic guanosine monophosphate (NO–cGMP) signaling and oxidative/mitochondrial processes in opioid tolerance paradigms. Preclinical evidence supports venlafaxine as a modulator of acute nociceptive control with notable opioid-interaction potential. Standardized pharmacodynamic reporting and translationally oriented studies are needed.

Background: Benzodiazepines and non-benzodiazepine hypnotics (Z-drugs) act at the benzodiazepine binding site of GABA_A receptors but differ in their receptor subtype selectivity and behavioural profiles. Diazepam acts as a non-selective positive allosteric modulator of benzodiazepine-sensitive GABA_A receptors, whereas zolpidem and indiplon display preferential affinity for α1-containing receptor subtypes. Although these compounds have been investigated individually in experimental models of exploratory behaviour and cognition, comparative behavioural data obtained using the same experimental protocol remain limited. Methods: This study evaluated the behavioural effects of diazepam, zolpidem and indiplon in male Wistar rats using a two-trial Y-maze paradigm with a 24 h retention interval. Animals received one of three dose levels of each compound before the acquisition trial. Recall-phase behaviour was evaluated using conventional exploration measures together with time- and entry-based preference indices for the previously inaccessible arm. Primary analyses were performed separately for each compound using one-way ANOVA with appropriate post hoc comparisons. Complementary exploratory factorial analyses were subsequently conducted to examine overall behavioural patterns across drug and nominal dose categories. Results: Diazepam produced marked dose-dependent reductions in recall-phase exploration of the previously inaccessible arm and in both exploratory preference indices. In contrast, zolpidem and indiplon reduced exploratory activity during the acquisition phase without significantly affecting recall-phase exploratory behaviour. The complementary factorial analyses identified significant Drug × Nominal Dose Categories interactions across all recall-related endpoints, indicating that behavioural responses across the nominal dose categories differed among the three compound-specific experimental series. The strongest interaction effects were observed for Time Index % (F(6,72) = 10.522, p < 0.001, ηp² = 0.467) and Entries Index % (F(6,72) = 6.870, p < 0.001, ηp² = 0.364). Conclusions: Diazepam produced more pronounced dose-dependent alterations in recall-phase exploratory behaviour than zolpidem or indiplon in the experimental conditions employed. The complementary factorial analyses support the interpretation that the three compounds exhibited different behavioural patterns across the nominal dose categories evaluated, while these exploratory comparisons should be interpreted within the constraints of the study design. Overall, the findings contribute to the comparative behavioural characterization of benzodiazepine-site modulators in the two-trial Y-maze paradigm.