scholarly journals CNS Opioid Signaling Separates Cannabinoid Receptor 1-Mediated Effects on Body Weight and Mood-Related Behavior in Mice

Endocrinology ◽  
2011 ◽  
Vol 152 (10) ◽  
pp. 3661-3667 ◽  
Author(s):  
Sarah Haas Lockie ◽  
Traci A. Czyzyk ◽  
Nilika Chaudhary ◽  
Diego Perez-Tilve ◽  
Stephen C. Woods ◽  
...  
Keyword(s):  
Body Weight ◽  
Side Effects ◽  
Opioid Receptor ◽  
Cannabinoid Receptor ◽  
Forced Swim Test ◽  
Inverse Agonist ◽  
Opioid System ◽  
Cannabinoid Receptor 1 ◽  
Immobility Time ◽  
Opioid Signaling

Existing monotherapies for the treatment of obesity provide only modest weight loss and/or have adverse side effects, and this is also the case with the cannabinoid receptor 1 (CB1) inverse agonist, rimonabant. We aimed to investigate the possibility of improving efficacy and reducing side effects of rimonabant by cotreatment with opioid system antagonists. Using both genetic and pharmacological removal of opioid signaling in mice, we investigated changes in body weight, food intake, and fat mass as well as behavioral outcomes of interactions between opioid ligands and the CB1 using the inverse agonist, rimonabant. The ability of rimonabant to reduce weight is enhanced by removal of with μ-opioid receptor signaling, while not being greatly affected by κ-opioid receptor blockade. Additionally, lack of opioid signaling, especially κ-opioid receptor, attenuated the ability of rimonabant to decrease immobility time in the Porsolt forced-swim test, a preclinical model of depression. These results indicate that the endogenous opioid system is involved in modulating both the metabolic and mood effects of rimonabant.

Cannabinoid receptor 1 antagonist treatment induces glucagon release and shows an additive therapeutic effect with GLP-1 agonist in diet-induced obese mice

2014 ◽  
Vol 92 (12) ◽  
pp. 975-983 ◽  
Author(s):  
Kartikkumar Navinchandra Patel ◽  
Amit Arvind Joharapurkar ◽  
Vishal Patel ◽  
Samadhan Govind Kshirsagar ◽  
Rajesh Bahekar ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Body Weight ◽  
Food Intake ◽  
Cannabinoid Receptor ◽  
Forced Swim Test ◽  
Conditioned Aversion ◽  
Serum Glucose ◽  
Body Weight Reduction ◽  
Glucagon Like Peptide 1

Cannabinoid 1 (CB1) receptor antagonists reduce body weight and improve insulin sensitivity. Preclinical data indicates that an acute dose of CB1 antagonist rimonabant causes an increase in blood glucose. A stable analog of glucagon-like peptide 1 (GLP-1), exendin-4 improves glucose-stimulated insulin secretion in pancreas, and reduces appetite through activation of GLP-1 receptors in the central nervous system and liver. We hypothesized that the insulin secretagogue effect of GLP-1 agonist exendin-4 may synergize with the insulin-sensitizing action of rimonabant. Intraperitoneal as well as intracerebroventricular administration of rimonabant increased serum glucose upon glucose challenge in overnight fasted, diet-induced obese C57 mice, with concomitant rise in serum glucagon levels. Exendin-4 reversed the acute hyperglycemia induced by rimonabant. The combination of exendin-4 and rimonabant showed an additive effect in the food intake, and sustained body weight reduction upon repeated dosing. The acute efficacy of both the compounds was additive for inducing nausea-like symptoms in conditioned aversion test in mice, whereas exendin-4 treatment antagonized the effect of rimonabant on forced swim test upon chronic dosing. Thus, the addition of exendin-4 to rimonabant produces greater reduction in food intake owing to increased aversion, but reduces the other central nervous system side effects of rimonabant. The hyperglucagonemia induced by rimonabant is partially responsible for enhancing the antiobesity effect of exendin-4.

scholarly journals The Cannabinoid Receptor 1 Reverse Agonist AM251 Ameliorates Radiation-Induced Cognitive Decrements

2021 ◽  
Vol 15 ◽  
Author(s):  
Vipan K. Parihar ◽  
Amber Syage ◽  
Lidia Flores ◽  
Angelica Lilagan ◽  
Barrett D. Allen ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Cannabinoid Receptor ◽  
Forced Swim Test ◽  
Memory Function ◽  
Cranial Irradiation ◽  
Hippocampal Neurogenesis ◽  
Neuronal Structure ◽  
Cannabinoid Receptor 1 ◽  
Beneficial Effects ◽  
Radiation Induced

Despite advancements in the radiotherapeutic management of brain malignancies, resultant sequelae include persistent cognitive dysfunction in the majority of survivors. Defining the precise causes of normal tissue toxicity has proven challenging, but the use of preclinical rodent models has suggested that reductions in neurogenesis and microvascular integrity, impaired synaptic plasticity, increased inflammation, and alterations in neuronal structure are contributory if not causal. As such, strategies to reverse these persistent radiotherapy-induced neurological disorders represent an unmet medical need. AM251, a cannabinoid receptor 1 reverse agonist known to facilitate adult neurogenesis and synaptic plasticity, may help to ameliorate radiation-induced CNS impairments. To test this hypothesis, three treatment paradigms were used to evaluate the efficacy of AM251 to ameliorate radiation-induced learning and memory deficits along with disruptions in mood at 4 and 12 weeks postirradiation. Results demonstrated that acute (four weekly injections) and chronic (16 weekly injections) AM251 treatments (1 mg/kg) effectively alleviated cognitive and mood dysfunction in cranially irradiated mice. The beneficial effects of AM251 were exemplified by improved hippocampal- and cortical-dependent memory function on the novel object recognition and object in place tasks, while similar benefits on mood were shown by reductions in depressive- and anxiety-like behaviors on the forced swim test and elevated plus maze. The foregoing neurocognitive benefits were associated with significant increases in newly born (doublecortin+) neurons (1.7-fold), hippocampal neurogenesis (BrdU+/NeuN+mature neurons, 2.5-fold), and reduced expression of the inflammatory mediator HMGB (1.2-fold) in the hippocampus of irradiated mice. Collectively, these findings indicate that AM251 ameliorates the effects of clinically relevant cranial irradiation where overall neurological benefits in memory and mood coincided with increased hippocampal cell proliferation, neurogenesis, and reduced expression of proinflammatory markers.

scholarly journals Cannabinoid Receptor 1 in the Vagus Nerve Is Dispensable for Body Weight Homeostasis But Required for Normal Gastrointestinal Motility

2012 ◽  
Vol 32 (30) ◽  
pp. 10331-10337 ◽  
Author(s):  
C. R. Vianna ◽  
J. Donato ◽  
J. Rossi ◽  
M. Scott ◽  
K. Economides ◽  
...  
Keyword(s):  
Body Weight ◽  
Vagus Nerve ◽  
Gastrointestinal Motility ◽  
Cannabinoid Receptor ◽  
Cannabinoid Receptor 1

scholarly journals UJI AKTIVITAS ANTIDEPRESAN PERASAN RIMPANG TEMULAWAK (Curcuma xanthorrhiza, Roxb) TERHADAP MENCIT PUTIH JANTAN (Mus musculus)

2019 ◽  
Vol 16 (01) ◽  
pp. 59
Author(s):  
Dian Kartikasari ◽  
Hairunisa Hairunisa ◽  
Emy Nadya Natasha
Keyword(s):  
Side Effects ◽  
Traditional Medicine ◽  
Mus Musculus ◽  
Forced Swim Test ◽  
Test Method ◽  
Antidepressant Effect ◽  
Swim Test ◽  
Forced Swim ◽  
Immobility Time ◽  
Ginger Rhizome

ABSTRACTPrevention and treatment with synthetic antidepressants has many side effects that affect the central nervous system and usage must be under the supervision of a doctor. Whereas prevention and traditional medicine relatively do not cause side effects, are inexpensive, and easy to obtain. One example of traditional medicine from natural ingredients, which can provide an antidepressant effect is ginger rhizome. This research aims to determine whether ginger rhizome have antidepressant effects on male white mice. Antidepressant effect testing was carried out on male white mice (Mus musculus) using the forced swim test method. The part of the plant used is the rhizome of the ginger plant. Curcuma rhizome is made with juice and given orally with a concentration of 20%, 40%, and 60%. The negative control used is Na CMC 0.5%, while the positive control used, namely amitriptilyn. The parameters observed were the duration of immobility time, swimming time and climibing time (in seconds) which were calculated from minutes 3-6 for 6 minutes, and statistical tests were carried out with a confidence level of 95%. The results showed that at a concentration of 40% the curcuma rhizome juice had a significant value (p> 0.05) which means that there was no significant difference in antidepressant effect (%) from the juice of temulawak 56.31% and amitriptylin 78.78%Keywords: ginger rhizome, antidepressants, the forced swim test

scholarly journals Antidepressant effects of an inverse agonist selective for α5 GABA-A receptors in the rat forced swim test

2014 ◽  
Vol 64 (1) ◽  
pp. 52-60 ◽  
Author(s):  
Janko Samardžić ◽  
Laslo Puškaš ◽  
Miljana Obradović ◽  
Dijana Lazić-Puškaš
Keyword(s):  
Locomotor Activity ◽  
Forced Swim Test ◽  
Digital Camera ◽  
Repeated Administration ◽  
Inverse Agonist ◽  
Gaba A ◽  
Swim Test ◽  
Forced Swim ◽  
Antidepressant Effects ◽  
Immobility Time

Abstract It has been shown in electrophysiological studies that the ligand L-655,708 possesses a binding selectivity and a moderate inverse agonist functional selectivity for α5-containing GABA-A receptors. The present study is aimed to investigate the antidepressant effects of the ligand L-655,708 in the forced swim test (FST) and its impact on locomotor activity in rats. The behavior of the animals was recorded with a digital camera, and the data were analyzed by one-way ANOVA, followed by Dunnett’s test. In FST, L-655,708 significantly decreased immobility time at a dose of 3 mg/kg after a single and repeated administration (p<0.05), exerting acute and chronic antidepressant effects. However, it did not induce significant differences in the time of struggling behavior during FST. Furthermore, L-655,708 did not show a significant effect on locomotor activity (p>0.05). These data suggest that negative modulation at GABA-A receptors containing the α5 subunit may produce antidepressant effects in rats. These effects were not confounded by locomotor influences.

scholarly journals Antidepressant-Like Effect of Terpineol in an Inflammatory Model of Depression: Involvement of the Cannabinoid System and D2 Dopamine Receptor

Biomolecules ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 792 ◽  
Author(s):  
Graziela Vieira ◽  
Juliana Cavalli ◽  
Elaine C. D. Gonçalves ◽  
Saulo F. P. Braga ◽  
Rafaela S. Ferreira ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Cannabinoid Receptor ◽  
D2 Receptor ◽  
Inverse Agonist ◽  
Control Group ◽  
Molecular Evidence ◽  
Acute Administration ◽  
Immobility Time ◽  
Cb2 Receptors ◽  
Cb1 And Cb2 Receptors

Depression has a multifactorial etiology that arises from environmental, psychological, genetic, and biological factors. Environmental stress and genetic factors acting through immunological and endocrine responses generate structural and functional changes in the brain, inducing neurogenesis and neurotransmission dysfunction. Terpineol, monoterpenoid alcohol, has shown immunomodulatory and neuroprotective effects, but there is no report about its antidepressant potential. Herein, we used a single lipopolysaccharide (LPS) injection to induce a depressive-like effect in the tail suspension test (TST) and the splash test (ST) for a preventive and therapeutic experimental schedule. Furthermore, we investigated the antidepressant-like mechanism of action of terpineol while using molecular and pharmacological approaches. Terpineol showed a coherent predicted binding mode mainly against CB1 and CB2 receptors and also against the D2 receptor during docking modeling analyses. The acute administration of terpineol produced the antidepressant-like effect, since it significantly reduced the immobility time in TST (100–200 mg/kg, p.o.) as compared to the control group. Moreover, terpineol showed an antidepressant-like effect in the preventive treatment that was blocked by a nonselective dopaminergic receptor antagonist (haloperidol), a selective dopamine D2 receptor antagonist (sulpiride), a selective CB1 cannabinoid receptor antagonist/inverse agonist (AM281), and a potent and selective CB2 cannabinoid receptor inverse agonist (AM630), but it was not blocked by a nonselective adenosine receptor antagonist (caffeine) or a β-adrenoceptor antagonist (propranolol). In summary, molecular docking suggests that CB1 and CB2 receptors are the most promising targets of terpineol action. Our data showed terpineol antidepressant-like modulation by CB1 and CB2 cannabinoid receptors and D2-dopaminergic receptors to further corroborate our molecular evidence.

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