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The frequency of spontaneous alternation in a Y-maze (visiting each arm in turn at p>50%) depends on the influence of the attention given to intra- and extra-maze cues. We examined the observing responses shown by rats (collateral rearing and head-turning behaviour), the habituation to the novelty and alternation responses over 15 minutes/day, four days in a row - in a Y-maze under enhanced and reduced dopamine (DA) activity (amphetamine- and haloperidol treatment). Methods: Prior to placement in a Y-maze for 15 minutes observation on 4 successive days animals were treated with either amphetamine (0.5 or 2.5 mg/kg) or pre-treated with a low dose of haloperidol (0.08 mg/kg, ip). Results: 1/ Amphetamine treated animals chose the arms at random on day 1, but after the higher dose on day 2-4 they perseverated their choice. The controls maintained their alternation over this period. 2/ The amphetamine-induced effects on alternation were prevented by prior treatment with the neuroleptic haloperidol. 3/ Amphetamine treatment increased the frequency of rearing in the middle at the choice point of the Y-maze. Haloperidol pre-treatment blocked this increase at the midpoint on day 1, and blocked the rearing behavior at the end of an arm on day 2. 4/ Amphetamine also increased the frequency of head turning and "looking", - an effect that was also prevented by haloperidol. (day 2 onwards). 5/ Haloperidol increased the duration of" looking" and of rearing at the end of an arm later in testing.. Conclusions: Two effects are postulated to have occurred. a) a conflict on day 1 between the novelty-controlled sensory or attentional effects, that leads to an alternation of arm-choice, and amphetamine-induced DA activity that facilitates an alternation of behavioural responses: -- the result was random choice and increased rearing at the choice point. b) On days 2-4 the drug-induced effects on switching motor responses came to control behaviour

The Study and the Method: The locomotor activity of adult male Sprague-Dawley was automatically recorded in a circular corridor - circadian changes are described as well as the response to the novel situation and its habituation over three hours. Four groups of animals were compared, - those with sham/vehicle operations and those with 6-OHDA dopamine (DA) depleting lesions in - the frontal cortex, the limbic septum, and the ventral tegmental area (VTA - A10). Results: 1/ Lesions of the VTA resulted in increased dark-phase activity, - and a large response to an apomorphine challenge in comparison to other lesion and control groups: 2/ Septal 6-OHDA lesions did not alter locomotion: 3/ After frontal DA depletion there was a small increase of locomotion after the apomorphine challenge, that might reflect increased receptor sensitivity in cortical or sub-cortical areas: (Table 1: HPLC measures of NA, DA and DOPAC for each group in the prefrontal cortex, septum and N. accumbens) Figure 1 illustrates the cumulative photocell counts per hour over 24 hours for the 4 groups:. Figure 2 illustrates the cumulative photocell counts every 10 minutes over 90 minutes post-apomorphine treatment - maximal at 20-30 minutes and habituating over 60 minutes (90 minutes for the VTA group): overall activity VTA >> Frontal > Septal > Controls. Conclusions: Along with correlations found for motor activity with cortical levels of DA and NA, these results are interpreted to support a role for DA, NA and the region of the frontal cortex in modulating locomotion that is primarily mediated by mesolimbic VTA - accumbens - DA activity.

The performance of rats on the conditioned blocking test (CB) of learned inattention was measured in a two-way shuttle avoidance task after sham and dopamine (DA) - depleting lesions of the frontal cortex, the limbic septum, and the ventral tegmental area (VTA - A10). Methods: Animals were trained on two sessions with tone and / or light as conditioned stimuli. One group was trained with both stimuli on both sessions. A second group was trained on the first session with one stimulus and on the second with both stimuli. The blocking of conditioning to the added stimulus (b) was tested by presenting the stimuli (a and b) separately and measuring the blocking ration (avoidance to b/a + b) and response latencies. Results: 1/ No deficits were recorded on tests of sensory and motor ability; 2/ The VTA group alone showed a hyperlocomotor response to apomorphine treatment, - and did not acquire the avoidance response (i.e. did not learn the active avoidance task); 3/ The appearance of blocking in the septally lesioned group was delayed until the end of the 20-trial test session - then it was exaggerated; 4/ Blocking was mildly attenuated in the frontally lesioned group. 5/ Dopamine (DA) levels were depleted by about 80% and noradrenaline (NA) levels by, respectively, 20% and 50% in the frontal and septal regions. Figure 2 illustrates a) the CB impairment in the frontal group relative to sham controls, and b) the late development of "supr-blocking" in septally-damage animals. Figure 3 illustrates the results of the HPLC analysis for NA, DA and DOPAC in frontal cortex, septum, N. accumbens and striatum after 6-OHDA lesions (& vehicle treatment) in the frontal, septal, and VTA areas. Conclusions: The results show that the levels of DA activity, or rather the balance between the activity of DA and NA in frontal and limbic regions can contribute to efficient associative conditioning and / or the normal ability of rats not to attend to a redundant stimulus.

This study was aimed at determining the phenolic composition and the antioxidant activity of leaves of Arbutus unedo populations belonging to seven Moroccan locations. Antioxidant activity is evaluated using two methods: scavenging effect on DPPH and scavenging effect on ABTS radicals. The Arbutus unedo leaf extracts displayed average values of 61.95 mg GAE, 3.60 mg QE, and 0.15 mg CE per g of dry weight (DW) in polyphenols, flavonoids, and tannins contents, respectively. All extracts exhibited a strong antioxidant effect on both assays, presenting mean IC50 values of 4.22 in DPPH assay and 4.86 μg/ml in ABTS assay. Significant variability (P < 0.0001) was showed among surveyed populations; samples from the Chefchaouen location (CH) was revealed the highest total phenolic content (107.67 mg GAE/g DW) and the strongest antioxidant activity (IC50 values of 0.80 and 1.56 μg/ml, in DPPH and ABTS tests, respectively). The phenolic profile achieved by HPLC-DAD-ESI/MS was dominated by gallic acid, Gallic acid glucose derivative, and Galloylquinic acid derivative. A significant negative correlation (P < 0.05) was observed between the total phenolic content and the antioxidant activity. These results provide that Arbutus unedo leaves should be considered as a promising source of natural antioxidants, and as ingredients in complimentary food and nutraceutical products. [ABSTRACT FROM AUTHOR]

Retama dasycarpa is an endemic shrubby leguminous plant of Morocco used in traditional folk medicine. The plant has never been studied for either its phytochemical or pharmacological properties. This study represents the first investigation of the phytochemical profile as well as the antioxidant, the antibacterial, the analgesic effects and the oral acute toxicity of Retama dasycarpa . Watery and hydromethanolic stems plant macerates have been investigated. Secondary metabolites quantitative analysis was achieved through spectrophotometric techniques. Antioxidant effect was explored through DPPH, ABTS and FRAP trials. Antibacterial activity was investigated using a micro-plates dilution assay. Analgesic activity was explored through acetic acid-induced writhing and tail-flick methods. Acute oral toxicity was investigated on mice. Phytochemical analysis was achieved through UHPLC connected to diode array and mass spectrometry detectors. The obtained results showed significant contents in total phenolics, flavonoids and tannins in both extracts especially the hydromethanolic extract whose contents were slighlty higher than the aqueous one resulting in a remarkable antioxidant activity. Compared to the aqueous extract, the H 2 O:MeOH (1:1) one showed notable antibacterial activity against the tested strains. The acute toxicity in mice revealed the non-toxicity of the extracts along with a promised starting material of central and peripheral analgesics. The UHPLC analysis revealed the presence of several bioactive phytochemicals pertaining to phenolic acids, flavonols, flavones and isoflavones. The obtained results demonstrate the richness of this endemic and unexplored plant in terms of bioactive compounds and their associated activities, making it a promising source of pharmacological ingredients., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:The author Nour Eddine ES-SAFI is an Associate Editor for Heliyon and was not involved in the editorial review or the decision to publish this article. This research was supported by ANPMA/UM5R/CNRST (Project number PMA2019-4). If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

Introduction: Aging is often linked to oxidative stress, where the body experiences increased damage from free radicals. Plants are rich sources of antioxidants, playing a role in slowing down aging and supporting the proper functioning and longevity of cells. Our study focuses on exploring the impact of Mentha rotundifolia (MR) and Salvia officinalis (SO) hydrosols on aging-related comorbidities., Methods: The chemical composition of MR and SO hydrosols was analyzed by gas chromatography coupled to mass spectrometry. 2,2-Diphenyl 1-picrylhydrazyl and 2,20-azino-bis 3-ethylbenzothiazoline-6-sulfonic acid radicals scavenging assays were used to assess their in vitro antioxidant activity, and heat induced albumin denaturation test was used to evaluate their anti-inflammatory activity. Subsequently, we administered 5% of each plant hydrosol in the drinking water of 18-month-old rats for six months. We then conducted behavioral tests, including open field, dark/light box, rotarod, and Y-maze assessments, and measured biochemical parameters in plasma, liver and brain tissues., Results and Discussion: At two years old, animals treated with MR and SO hydrosols displayed fewer physical and behavioral impairments, along with well-preserved redox homeostasis in comparison with animals in the control group. These results highlighted the significance of MR and SO hydrosols in addressing various aspects of age-related comorbidities. The study suggests that these plant-derived hydrosols may have potential applications in promoting healthy aging and mitigating associated health challenges., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Boualam, Ibork, Lahboub, Sobeh and Taghzouti.)

Chronic exposure to cocaine is known to have profound effects on the brain, leading to the dysregulation of inflammatory signalling pathways, the activation of microglia, and the manifestation of cognitive and motivational behavioural impairments. The endocannabinoid system has emerged as a potential mediator of cocaine's deleterious effects. In this study, we sought to investigate the therapeutic potential of the cannabinoid CB2 receptor agonist, JWH-133, in mitigating cocaine-induced inflammation and associated motivational behavioural alterations in an in vivo model. Our research uncovered compelling evidence that JWH-133, a selective CB2 receptor agonist, exerts a significant dampening effect on the reinstatement of cocaine-induced conditioned place preference. This effect was accompanied by notable changes in the neurobiological landscape. Specifically, JWH-133 administration was found to upregulate Δ-FOSB expression in the nucleus accumbens (Nac), elevate CX3CL1 levels in both the ventral tegmental area and prefrontal cortex (PFC), and concurrently reduce IL-1β expression in the PFC and NAc among cocaine-treated animals. These findings highlight the modulatory role of CB2 cannabinoid receptor activation in altering the reward-seeking behaviour induced by cocaine. Moreover, they shed light on the intricate interplay between the endocannabinoid system and cocaine-induced neurobiological changes, paving the way for potential therapeutic interventions targeting CB2 receptors in the context of cocaine addiction and associated behavioural deficits., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Cerebral metabolic abnormalities are common in neurodegenerative diseases. Previous studies have shown that mitochondrial damage alters ATP production and increases reactive oxygen species (ROS) release which may contribute to neurodegeneration. In the present study, we investigated the neuroprotective effects of cannabidiol (CBD), a non-psychoactive component derived from marijuana (Cannabis sativa L.), on astrocytic bioenergetic balance in a primary cell culture model of lipopolysaccharide (LPS)-induced neurotoxicity. Astrocytic metabolic profiling using an extracellular flux analyzer demonstrated that CBD decreases mitochondrial proton leak, increased spare respiratory capacity and coupling efficiency in LPS-stimulated astrocytes. Simultaneously, CBD increased astrocytic glycolytic capacity and glycolysis reserve in a cannabinoid receptor type 1 (CB1)-dependent manner. CBD-restored metabolic changes were correlated with a significant decrease in the pro-inflammatory cytokines tumor necrosis factor α (TNFα) and interleukin-6 (IL-6) concentration and reduction of ROS production in LPS-stimulated astrocytes. These results suggest that CBD may inhibit LPS-induced metabolic impairments and inflammation by enhancing astrocytic metabolic glycolysis versus oxidative phosphorylation through its action on CB1 receptors. The present findings suggest CBD as a potential anti-inflammatory treatment in metabolic pathologies and highlight a possible role for the cannabinoidergic system in the modulation of mitochondrial oxidative stress. CBD enhances mitochondrial bioenergetic profile, attenuates proinflammatory cytokines release, and ROS overproduction of astrocytes stimulated by LPS. These effects are not mediated directly by CB1 receptors, while these receptors seem to have a key role in the anti-inflammatory response of the endocannabinoid system on astrocytes, as their specific inhibition by SR141716A led to increased pro-inflammatory cytokines release and ROS production. The graphical abstract is created with BioRender.com., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)