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We substantiated the effect of AM251, a cannabinoid receptor-1 (CB1R) antagonist, against β-receptor stimulated myocardial infarction (MI) in streptozotocin (STZ)-induced diabetic mice via modulation- of the NF-kB signaling pathway. The different parameters were assessed such as ECG, hemodynamic, cardiac injury markers, oxidative stress parameters, pro-inflammatory cytokines, and histopathological abnormalities. Mice were fed a high-fat diet for 30 days. On day 7, to trigger diabetes, 150 mg/kg of STZ was injected intraperitoneally. On day 10, to determine whether diabetes developed, the blood level of glucose was monitored. From days 11-30, diabetic mice were injected with either CB1R agonist oleamide or antagonist AM251 or both, with concurrent administrations of β-agonist isoproterenol on days 28 and 29 to induce MI. In comparison to normal, the myocardial infarcted diabetic animals demonstrated alterations in ECG, hemodynamic profiles, and diminished enzymatic activities (CK-MB, LDH, SOD, GSH, catalase), with concurrently increased MDA levels, which indicated increased oxidative stress in the myocardium. Additionally, higher concentrations of cytokines that signal myocardial inflammation, such as IL-1β, IL-6, and TNF-α, were also noted. Furthermore, elevated myonecrosis, edema, and cell infiltration which is confirmed by histopathology of heart tissue. Treatment with AM251 significantly ameliorated myocardial redox status, reduced cytokines, and repaired enzymatic activities leading to subsequent recovery in cardiac function. AM251 effectively suppressed myonecrosis and edema. This study also showed that AM251 protects against myocardial inflammation and oxidative stress triggered by isoproterenol by blocking NF-kB signalling pathway. However, upregulation of the CB1R through oleamide showed significant cardiac toxicity. Conversely, the concurrent administration of oleamide and AM251 failed to induce cardiotoxic effects in isoproterenol-induced MI in diabetic mice which indicates downregulation of the CB1R might be associated with the cardioprotective effect., Competing Interests: The authors 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.)

The lipid endocannabinoid system has recently emerged as a novel therapeutic target for several inflammatory and tissue-damaging diseases, including those affecting the cardiovascular system. The primary targets of cannabinoids are cannabinoid type 1 (CB1) and 2 (CB2) receptors. The CB2 receptor is expressed in the cardiomyocytes. While the pathological changes in the myocardium upregulate the CB2 receptor, genetic deletion of the receptor aggravates the changes. The CB2 receptor plays a crucial role in attenuating the advancement of myocardial infarction (MI)-associated pathological changes in the myocardium. Activation of CB2 receptors exerts cardioprotection in MI via numerous molecular pathways. For instance, delta-9-tetrahydrocannabinol attenuated the progression of MI via modulation of the CB2 receptor-dependent anti-inflammatory mechanisms, including suppression of pro-inflammatory cytokines like IL-6, TNF-α, and IL-1β. Through similar mechanisms, natural and synthetic CB2 receptor ligands repair myocardial tissue damage. This review aims to offer an in-depth discussion on the ameliorative potential of CB2 receptors in myocardial injuries induced by a variety of pathogenic mechanisms. Further, the modulation of autophagy, TGF-β/Smad3 signaling, MPTP opening, and ROS production are discussed. The molecular correlation of CB2 receptors with cardiac injury markers, such as troponin I, LDH1, and CK-MB, is explored. Special attention has been paid to novel insights into the potential therapeutic implications of CB2 receptor activation in MI.

Neuroinflammation is a complex biological process that typically originates as a protective response in the brain. This inflammatory process is triggered by the release of pro-inflammatory substances like cytokines, prostaglandins, and reactive oxygen and nitrogen species from stimulated endothelial and glial cells, including those with pro-inflammatory functions, in the outer regions. While neuronal inflammation is common in various central nervous system disorders, the specific inflammatory pathways linked with different immune-mediated cell types and the various factors influencing the blood-brain barrier significantly contribute to disease-specific characteristics. The endocannabinoid system consists of cannabinoid receptors, endogenous cannabinoids, and enzymes responsible for synthesizing and metabolizing endocannabinoids. The primary cannabinoid receptor is CB1, predominantly found in specific brain regions such as the brainstem, cerebellum, hippocampus, and cortex. The presence of CB2 receptors in certain brain components, like cultured cerebellar granular cells, Purkinje fibers, and microglia, as well as in the areas like the cerebral cortex, hippocampus, and cerebellum is also evidenced by immunoblotting assays, radioligand binding, and autoradiography studies. Both CB1 and CB2 cannabinoid receptors exhibit noteworthy physiological responses and possess diverse neuromodulatory capabilities. This review primarily aims to outline the distribution of CB1 and CB2 receptors across different brain regions and explore their potential roles in regulating neuroinflammatory processes.

Natural polysaccharides have been widely exploited in drug delivery and tissue engineering research. They exhibit excellent biocompatibility and fewer adverse effects; however, it is challenging to assess their bioactivities to that of manufactured synthetics because of their intrinsic physicochemical characteristics. Studies showed that the carboxymethylation of polysaccharides considerably increases the aqueous solubility and bioactivities of inherent polysaccharides and offers structural diversity, but it also has some limitations that can be resolved by derivatization or the grafting of carboxymethylated gums. The swelling ratio, flocculation capacity, viscosity, partition coefficient, metal absorption properties, and thermosensitivity of natural polysaccharides have been improved as a result of these changes. In order to create better and functionally enhanced polysaccharides, researchers have modified the structures and properties of carboxymethylated gums. This review summarizes the various ways of modifying carboxymethylated gums, explores the impact that molecular modifications have on their physicochemical characteristics and bioactivities, and sheds light on various applications for the derivatives of carboxymethylated polysaccharides.

Objectives: In the era of globalization, a sedentary lifestyle is highly linked with obesity and neurobehavioral complications such as depression. While depression is associated with dopamine dysfunction in the ventral tegmental area (VTA), ghrelin enhances the dopaminergic activity in the VTA. Therefore, the present study aimed to assess the effect of ghrelin on depression-like behaviour in rats subjected to a high-fat diet (HFD) and disturbed diurnal rhythm (DDR) for 45 days., Methods: The neurobehavioral deficits resulting from HFD and DDR in rats, and the behaviour modulation by intra-VTA administration of ghrelin, alone or in combination with ghrelin receptor antagonist were confirmed by evaluation of behavioural parameters in the elevated plus-maze, forced swim test, open field test, and rotarod assessment. Further, the levels of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and IL-6, oxidative stress marker malondialdehyde (MDA), and antioxidants enzymes like superoxide dismutase (SOD), reduced glutathione (GSH), and catalase (CAT) were measured., Results: The levels of TNF-α, IL-1β, IL-6, and MDA were increased in the brain of HFD and DDR exposed rats, while that of SOD, GSH, and CAT were reduced. Intra-VTA ghrelin administration from day 41-45 to the HFD and DDR exposed rats improved cognitive behaviour and physical activity confirming the antidepressant effect. Moreover, ghrelin restored the levels of SOD, GSH and CAT efficiently, and reduced that of MDA, TNF-α, IL-1β and IL-6, which signifies its protective effect., Conclusion: Overall, this study confirmed the ameliorative effect of ghrelin in HFD- and DDR-induced depression-like behaviour., Competing Interests: None., (AJTR Copyright © 2022.)

Phloretin is a flavonoid of the dihydrogen chalcone class, present abundantly in apples and strawberries. The beneficial effects of phloretin are mainly associated with its potent antioxidant properties. Phloretin modulates several signaling pathways and molecular mechanisms to exhibit therapeutic benefits against various diseases including cancers, diabetes, liver injury, kidney injury, encephalomyelitis, ulcerative colitis, asthma, arthritis, and cognitive impairment. It ameliorates the complications associated with diabetes such as cardiomyopathy, hypertension, depression, memory impairment, delayed wound healing, and peripheral neuropathy. It is effective against various microbial infections including Salmonella typhimurium , Listeria monocytogenes , Mycobacterium tuberculosis , Escherichia coli , Candida albicans and methicillin-resistant Staphylococcus aureus . Considering the therapeutic benefits, it generated interest for the pharmaceutical development. However, poor oral bioavailability is the major drawback. Therefore, efforts have been undertaken to enhance its bioavailability by modifying physicochemical properties and molecular structure, and developing nanoformulations. In the present review, we discussed the pharmacological actions, underlying mechanisms and molecular targets of phloretin. Moreover, the review provides insights into physicochemical and pharmacokinetic characteristics, and approaches to promote the pharmaceutical development of phloretin for its therapeutic applications in the future. Although convincing experimental data are reported, human studies are not available. In order to ascertain its safety, further preclinical studies are needed to encourage its pharmaceutical and clinical development.

Earlier studies reported that long-term treatment with thymoquinone (TQ) at a high dose (20 mg/kg) exerts a cardioprotective effect against isoproterenol (ISO)-triggered myocardial infarction (MI) in rats. In the present study, we tested the hypothesis that TQ, as a potent molecule, can exhibit cardioprotective effects at the lower dose for a short-term regimen. The rats were administered with TQ (5 mg/kg, intraperitoneal) at the 4 h interval for 2 days. ISO (100 mg/kg/day, subcutaneous) was given for 2 days to produce MI. ISO challenge results in deformation in ECG wave front, elevated left ventricular (LV) end-diastolic pressure, and reduced LVdP/dtmax and LVdP/dtmin. The levels of the cardiac biomarker in serum, such as creatine kinase MB, alanine aminotransferase, and aspartate aminotransferase, were increased. In the myocardium, a rise in malonaldehyde and decreased superoxide dismutase, glutathione, and catalase contents were observed. Furthermore, increased levels of tumor necrotic factor-α, interleukin-6, and interleukin-1β were observed in the myocardium. TQ pretreatment significantly normalized alterations in hemodynamic parameters, strengthened the antioxidant defense system, and decreased the contents of pro-inflammatory cytokines and hepatic enzymes as compared to the ISO group. Based on the results, TQ appears to be cardioprotective at low doses, and effective even administered for a shorter duration.

Ghrelin is a peptide released by the endocrine cells of the stomach and the neurons in the arcuate nucleus of the hypothalamus. It modulates both peripheral and central functions. Although ghrelin has emerged as a potent stimulator of growth hormone release and as an orexigenic neuropeptide, the wealth of literature suggests its involvement in the pathophysiology of affective disorders including depression. Ghrelin exhibits a dual role through the advancement and reduction of depressive behavior with nervousness in the experimental animals. It modulates depression-related signals by forming neuronal networks with various neuropeptides and classical neurotransmitter systems. The present review emphasizes the integration and signaling of ghrelin with other neuromodulatory systems concerning depressive disorders. The role of ghrelin in the regulation of neurosynaptic transmission and depressive illnesses implies that the ghrelin system modulation can yield promising antidepressive therapies., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Molecular docking revealed curcumin as a potent CB2 cannabinoid receptor (CB2R) agonist. Since CB2R is involved in cardioprotective functions, we explored its role in ameliorative actions of curcumin against myocardial damage triggered by isoproterenol in diabetic animals. Mice were kept on a high-fat diet (HFD) throughout the experiment (30 days). Following 7 days of HFD feeding, streptozotocin was administered (150 mg/kg, intraperitoneal) to induce diabetes. From day 11 to 30, diabetic mice received either curcumin (100 or 200 mg/kg/day, oral), CB2R antagonist AM630 (1 mg/kg/day, intraperitoneal) or both, with concurrent isoproterenol (150 mg/kg, subcutaneous) administration on day 28 and 29. Diabetic mice with myocardial infarction showed an altered hemodynamic pattern and lipid profile, reduced injury markers, antioxidants with increased lipid peroxidation in the myocardium, and elevated glucose and liver enzymes in the blood. Moreover, an increased pro-inflammatory markers, histological severity, myonecrosis, and edema were observed. Curcumin compensated for hemodynamic fluctuations, restored biochemical markers, preserved antioxidant capacity, decreased cytokines levels, and restored cardiac functionality. However, the AM630 pre-treatment attenuated the effects of curcumin. The data suggest the involvement of CB2R in the actions of curcumin such as in the prevention of myocardial stress and in the improvement of the normal status of the myocardial membrane associated with diabetes.

Anemia is the most common hematological abnormality of chemotherapy, which is responsible for poor clinical outcomes. To overcome this complication, the present study was aimed for developing a Eudragit/polylactic-co-glycolic acid (PLGA) based nanoparticulate system for a model drug paclitaxel (PTX). The study was planned using a simplex lattice mixture design. PTX nanoparticles (PTXNp) were evaluated in vitro for physicochemical properties, hemolytic effects and cytotoxic effects. Further, the nanoparticles were subjected to in vivo screening using rats for hemocompatibility, pharmacokinetic profile, and biodistribution to the vital organs. The PTXNps were 65.77-214.73 nm in size, showed more than 60% sustained drug release in 360 h and caused less than 8% hemolysis. The parameters like red blood cell count, activated partial thromboplastin time (aPTT), prothrombin time (PT) and C3 complement were similar to the negative control. Cytotoxicity results suggested that all the PTXNp demonstrated drug concentration-dependent cytotoxicity. The in vivo pharmacokinetic study concluded that PTXNp formulations had significantly higher blood AUC (93.194.55-163,071.15 h*ng/mL), longer half-lives (5.80-6.35 h) and extended mean residence times (6.05-8.54 h) in comparison to PTX solution (p < 0.05). Overall, the study provides a nanoparticulate drug delivery system to deliver PTX safely and effectively along with reducing the associated hematological adverse effects., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

The proposed study involves delivering drug/bioactive using a single nanoplatform based on poly lactic-co-glycolic acid (PLGA) for better efficacy, synergistic effect, and reduced toxicity. PLGA was conjugated to doxorubicin (D1), and this conjugate was used for encapsulation of naringenin (D2) to develop naringenin loaded PLGA-doxorubicin nanoparticles (PDNG). The PDNG NPs were 165.4 ± 4.27 nm in size, having 0.112 ± 0.035 PDI, with -10.1 ± 2.74 zeta potential. The surface morphology was confirmed through transmission electron microscopy (TEM) and atomic force microscopy (AFM). The in vitro studies revealed that PDNG NPs exhibited selective anticancer potential in breast cancer cells, and induced apoptosis with S-phase inhibition via an increase in intrinsic reactive oxygen species (ROS) and altering the mitochondrial potential. The results also signified the efficient uptake of nanoparticles encapsulated drugs by cells besides elevating the caspase level suggesting programmed cell death induction upon treatment. In vivo studies results revealed better half-life (27.35 ± 1.58 and 11.98 ± 1.21 h for doxorubicin and naringenin) with higher plasma drug concentration. In vivo biodistribution study was also in accordance with the in vitro studies and in line with the in vivo pharmacokinetic. In vivo tumor regression assay portrayed that the formulation PDNG halts the tumor growth and lessen the tumor volume with the stable bodyweight of the mice. Conclusively, the dual delivery approach was beneficial and highly effective against tumor-induced mice., Competing Interests: The authors declare no competing financial interest., (© 2021 The Author(s).)

Background and Aim: Flavonoid rich plant Tephrosia purpurea ( T. purpurea ), commonly known as Sarpunkha has been used in traditional systems of medicine to treat diabetes mellitus. However, its effectiveness in promoting regeneration of pancreas in diabetes has not been investigated. Therefore, the present study was undertaken to evaluate pancreatic β-cells regeneration, antioxidant and antihyperlipidemic potentials of T. purpurea leaves extract, its fractions and main constituent Rutin in diabetic rats., Experimental Procedure: The leaves extract and its fractions were first screened for acute and sub-chronic antidiabetic activity in a dose range of 250-500 mg/kg orally. Further, fractions with potent antidiabetic activity were screened for pancreatic β-cells regeneration activity using histopathological studies and morphometric analysis, which was followed by estimation of biochemical parameters., Results and Conclusion: The most significant antidiabetic, pancreatic regeneration and antihyperlipidemic activity was exhibited by n -butanol soluble fraction of ethanol extract at the dose level of 500 mg/kg. Histopathology revealed that treatment with this fraction improved the β-cell granulation of islets and prevented the β-cells damage which was further confirmed by morphometric analysis. Thus, the present study validated the traditional use of T. purpurea plant in the treatment of diabetes, which might be attributed to pancreatic β-cells regeneration potential of its active constituent Rutin., Taxonomy Classification by Evise: Traditional Medicine; Metabolic Disorder; Experimental Design; Cell Regeneration and Histopathology., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 Center for Food and Biomolecules, National Taiwan University. Production and hosting by Elsevier Taiwan LLC.)

Background: Lipopolysaccharide (LPS) is known to produce neuroinflammation and memory impairment. Although phloridzin (a phenolic phytoconstituent) shows antioxidant- and anti-inflammatory activities, its ameliorative potential in LPS-mediated neuroinflammation and memory dysfunction remains unexplored., Objectives: To investigate the protective effect of phloridzin against LPS-mediated memory impairment and neuroinflammation in mice., Methods: Different groups of mice were treated with LPS (250 μg/kg) via intraperitoneal (ip) route to induce cognitive impairments. The animals were administered with phloridzin (10-20 mg/kg, oral) or donepezil (1 mg/kg, intraperitoneal), and memory functions were evaluated by Morris water maze (MWM) and Y-maze. At the end of the behavioral experiments, the animals were sacrificed and different biochemical parameters like acetylcholinesterase (AChE), brain derived neurotropic factor (BDNF), tumor necrosis factor (TNF-α), interleukin-6 (IL-6), superoxide dismutase (SOD) and glutathione (GSH) concentration in the hippocampus and the cerebral cortex were estimated., Results: While LPS administered animals showed significantly decreased memory retention in both MWM and Y maze, a significant reversal in all the parameters were observed following treatment with phloridzin. LPS-treated animals showed significantly decreased level of antioxidants (SOD and GSH), neurotropic factor (BDNF) and cholinergic transmission (increased AChE) and increased levels of inflammatory/oxidative markers (TNF-α, IL-6 and MDA) in hippocampus and cortex. These changes were alleviated after the treatment with phloridzin., Conclusions: Phloridzin may have neuroprotective role against LPS-induced neuroinflammation and memory impairment by virtue of its antioxidant, anti-inflammatory, and enhanced cholinergic signalling activity in the hippocampus and cerebral cortex., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Purpose: Type 2 diabetes (T2D) is linked with depression due to insulin resistance, oxidative stress and disruption of neurotrophic factors. We evaluated potential benefits of phloridzin in ameliorating depressive symptoms in T2D., Methods: Adult male Swiss-albino mice (25-30 g) on high-fat-diet (HFD) for 2 weeks were administered with streptozotocin (STZ; 35 mg/kg, intraperitoneal) to induce T2D. Seven days after STZ administration, diabetic mice on HFD were distributed into different groups. Animals were subjected daily to oral treatment of saline (0.25 ml), fluoxetine (10-20 mg/kg) or phloridzin (10-20 mg/kg) for a period of 4 weeks. One hour after last dose, the immobility time of animals was evaluated in forced swim test (FST) and tail suspension test (TST). To further confirm the mechanisms involved in antidepressant effect of phloridzin, biochemical parameters like brain derived neurotropic factor (BDNF), glutathione (GSH), extracellular signal-regulated kinase (ERK), tyrosine receptor kinase B (TrkB) and cAMP-response element binding protein (CREB) were estimated in the brain., Results: Animals with T2D showed a significant increase in immobility as compared to control in FST and TST. However, 4 weeks administration of fluoxetine or phloridzin attenuated this effect. A significant decline in GSH, BDNF, TrkB, CREB and ERK levels were noticed in the brain of mice with T2D. These changes were also attenuated by administration of phloridzin., Conclusions: Phloridzin may ameliorates T2D-induced depression by mitigating the oxidative stress, and up-regulation of neurotrophins in the brain. Therefore, phloridzin can be used as a therapeutic intervention for the management of depression co-morbid with T2D., Competing Interests: Conflict of interestNone., (© Springer Nature Switzerland AG 2021.)

Purpose: Diabetic peripheral neuropathy (DPN) affects up to 50 % diabetic patients. Moreover, uncontrolled diabetes associated with impaired wound healing. The present study was aimed at exploring the effect of apple peel extract (APE) on type 2 diabetes (T2D)-induced DPN and delayed wound healing., Methods: In adult male Sprague-Dawley rats on high-fat diet, a single low dose streptozotocin (STZ, 35 mg/kg) was administered via intraperitoneal route to induce T2D. Plantar test using Hargreaves apparatus was used to evaluate the DPN. Six different groups of rats were treated orally with saline (naïve control and DPN control), APE (100, 200 and 400 mg/kg) and gabapentin (30 mg/kg) daily for 7 consecutive days and thermal paw withdrawal latency (PWL) was measured. To elucidate the underlying antioxidant effect of APE, the catalase (CAT), glutathione (GSH) and malonaldehyde (MDA) levels were measured. To evaluate the wound healing potential of APE, excision ischemic open wound model was used. Six different groups of rats were applied with 2 % gum acacia (naïve control and diabetic control), 1 % silver sulfadiazine (SSD) cream and APE cream (5, 10 and 20 %) twice daily for 28 days. Dry connective tissue parameters like hydroxyproline and hexosamine were also measured to further confirm the wound healing activity., Results: Diabetes produced thermal hyperalgesia in rats with a significant decrease in PWL as compared to naive controls indicating induction of DPN. APE and gabapentin significantly improved PWL in diabetic animals. Biochemical analysis revealed a significant improvement in oxidative stress parameters such as catalase, GSH and MDA. Wound closure was significantly more after day 15 of topical application of APE and SSD as compared to control group. APE significantly increased hydroxyproline and hexosamine levels as compared to standard cream. Moreover, histopathology revealed that, topical application of APE cream showed an enhanced healing process., Conclusions: On the basis of the findings, we conclude that APE has a potential to be used as a therapeutic intervention for the management of DPN and delayed wound healing in the diabetic condition., Competing Interests: Conflict of interestThere are no conflict of interest., (© Springer Nature Switzerland AG 2021.)

Streptozotocin (STZ) has been extensively used over the last three decades to induce diabetes in various animal species and to help screen for hypoglycemic drugs. STZ induces clinical features in animals that resemble those associated with diabetes in humans. For this reason STZ treated animals have been used to study diabetogenic mechanisms and for preclinical evaluation of novel antidiabetic therapies. However, the physiochemical characteristics and associated toxicities of STZ are still major obstacles for researchers using STZ treated animals to investigate diabetes. Another major challenges in STZ-induced diabetes are sustaining uniformity, suitability, reproducibility and induction of diabetes with minimal animal lethality. Lack of appropriate use of STZ was found to be associated with increased mortality and animal suffering. During STZ use in animals, attention should be paid to several factors such as method of preparation of STZ, stability, suitable dose, route of administration, diet regimen, animal species with respect to age, body weight, gender and the target blood glucose level used to represent hyperglycemia. Therefore, protocol for STZ-induced diabetes in experimental animals must be meticulously planned. This review highlights specific skills and strategies involved in the execution of STZ-induced diabetes model. The present review aims to provide insight into diabetogenic mechanisms of STZ, specific toxicity of STZ with its significance and factors responsible for variations in diabetogenic effects of STZ. Further this review also addresses ways to minimize STZ-induced mortality, suggests methods to improve STZ-based experimental models and best utilize them for experimental studies purported to understand diabetes pathogenesis and preclinical evaluation of drugs., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Introduction: Stereotaxic administration of neuroactive agents, either in ventricles, or targeted at specific intracranial sites, is a widely employed strategy for neurological studies in rodents. Surgical implantation of cannula on the skull is particularly useful in chronic treatments. We describe a simple, inexpensive and reliable method to fabricate a cannula system for delivery of drugs at the targeted sites in the brain of rat or mouse., Methods: The system consists of a guide cannula made from a hypodermic needle (24 gauge), a stainless steel wire (30 gauge) that serves as a dummy cannula, and an internal cannula made of stainless steel needle (30 gauge) taken from a hypodermic syringe. The cannula can be implanted by routine stereotaxic procedure and used for acute or chronic drug administration to conscious, free moving animals., Results: With a view to test the system for accuracy, the guide cannula was stereotaxically implanted, and neuropeptide Y was directly delivered into the lateral ventricle. These rats showed a significant increase in food intake. Another set of rats were cannulated for chronic protocol, wherein ethanol was delivered directly into the ventral tegmental area. In operant chamber, these rats showed increased ethanol self-administration. The proposed cannula takes around 5 min to fabricate and costs less than a dollar., Conclusion: We feel that it may serve as an economical and reliable tool in neuropharmacological and neurobehavioral studies., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objective: Although hyperphagia and body weight gain are well-recognized consequences of social isolation, the underlying mechanisms are not understood. The aim of this work is to test the possibility that the endogenous cocaine- and amphetamine-regulated transcript peptide (CART) may be involved in the process., Design: Socially isolated rats were screened for increase in food intake and body weight, and the modifications of these parameters by CART were evaluated. Furthermore, isolated animals were re-socialized and screened for reversal of these effects. Response of the endogenous CART system, in certain hypothalamic nuclei of the isolated and re-socialized rats, was evaluated with immunohistochemistry., Subjects: Fifty days old naive male Sprague-Dawley rats were used., Measurements: The effects of CART/CART antibody on the social isolation and subsequent re-socialization on feeding and body weight changes were monitored. Moreover, the immunohistochemical response of endogenous CART system to social isolation and re-socialization was analyzed morphometrically., Results: While social isolation of rats for a period of 6 weeks caused progressive increase in food consumption and body weight gain, these rats showed a significant reduction in food intake and body weight when injected daily with CART via intracerebroventricular (i.c.v.) route, for the following 7 days. The re-socialization of isolated rats reduced food intake and body weight to the control levels. These effects of re-socialization were attenuated by immunoneutralization of the endogenous CART by i.c.v. CART antibody. Social isolation also resulted in a drastic reduction in CART immunoreactivity in the cells and/or fibers in the hypothalamic areas like dorsomedial, ventromedial, lateral, paraventricular and arcuate nuclei, recognized for their role in feeding. On the other hand, the CART immunoreactivity profile was fully restored following 7 days of re-socialization of the isolation-reared rats., Conclusion: Social isolation might down-regulate the hypothalamic CART-containing system, which in turn may lead to increase in food intake and body weight.