Binge alcohol (ethanol) drinking is associated with profound adverse effects on our health and society. Rimonabant (SR141716A), a CB1 receptor inverse agonist, was previously shown to be effective for nicotine cessation and obesity. However, studies using rimonabant were discontinued as it was associated with an increased risk of depression and anxiety. In the present study, we examined the pharmacokinetics and effects of AM4113, a novel CB1 receptor neutral antagonist on binge-like ethanol drinking in C57BL/6J mice using a two-bottle choice drinking-in-dark (DID) paradigm. The results indicated a slower elimination of AM4113 in the brain than in plasma. AM4113 suppressed ethanol consumption and preference without having significant effects on body weight, ambulatory activity, preference for tastants (saccharin and quinine) and ethanol metabolism. AM4113 pretreatment reduced ethanol-induced increase in dopamine release in nucleus accumbens. Collectively, these data suggest an important role of CB1 receptor-mediated regulation of binge-like ethanol consumption and mesolimbic dopaminergic signaling, and further points to the potential utility of CB1 neutral antagonists for the treatment of binge ethanol drinking.

Major depressive disorder (MDD) is common, often under-treated and a leading cause of disability and mortality worldwide. The causes of MDD remain unclear, including the role of the endocannabinoid system. Intriguingly, the prevalence of depression is significantly greater in women than men. In this study we examined the role of endocannabinoids in depressive behavior. The levels of endocannabinoids, N-arachidonoyl ethanolamide (AEA) and 2-arachidonoyl glycerol (2-AG) were measured along with brain derived neurotrophic factor (BDNF) in postmortem ventral striata of female patients with MDD and non-psychiatric controls, and in Wistar Kyoto (WKY) rat, a selectively inbred strain of rat widely used for testing the depressive behavior. The effect of pharmacological elevation of endocannabinoids through inhibition of their catabolizing enzymes (fatty acid amide hydrolase [FAAH] and monoacyl glycerol lipase [MAGL]) on depressive-like phenotype was also assessed in WKY rat. The findings showed lower levels of endocannabinoids and BDNF in the ventral striatum of MDD patients and WKY rats. A dual inhibitor of FAAH and MAGL, JZL195, elevated the endocannabinods and BDNF levels in ventral striatum, and reduced the depressive-like phenotype in female WKY rats. Collectively, our study

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In this work, we reported the successful synthesis of novel Ag/TiO2/CuFe2O4 ternary nanocomposite by hydrothermal technique by using TiO2/CuFe2O4 binary nanocomposite precursor that was also prepared by hydrothermal treatment by using TiO2 nanoparticles and CuFe2O4 nanoparticles synthesized via sol–gel method. The synthesized nanomaterials were accessed for their morphological, structural, and optical properties. X‐ray diffraction (XRD) study reveals the formation of pure Ag/TiO2/CuFe2O4 ternary nanocomposite in which the Ag, TiO2, and CuFe2O4 are in anatase, spinal, and cubic crystal phases, respectively. Transmission electron microscopy (TEM) and high‐resolution TEM (HRTEM) analyses of Ag/TiO2/CuFe2O4 ternary nanocomposite indicated granule‐shaped morphology with bright spots of silver. The existence of Ti, O, Cu, Fe, and Ag without any other elements in the energy‐dispersive X‐ray spectroscopy (EDS) spectra of the prepared ternary nanocomposite depict its purity and its polycrystalline nature was confirmed by its selected area electron diffraction (SAED) pattern. The ternary nanocomposite was utilized for the methylene blue dye degradation with an optimum dose of 1.00 g/100 ml under ultraviolet (UV) light; the enhanced photocatalytic activity of the composite is attributed mainly due to the appreciable magnitudinal difference of positive charge of the valence band and negative charge of the conduction band of TiO2 and CuFe2O4; meanwhile, the interfacially placed Ag acts as a sink for the elections. Also, the ternary nanocomposite showed satisfactory antibacterial activities. Practitioner Points The prepared ternary nanocomposite showed effective results in dye degradation and satisfactory antibacterial property. The concentration of methylene dye has decreased considerably in every degradation process which was accessed through UV‐vis studies. The highest degradation by using the ternary nanocomposite archived at pH = 6 Appreciable antibacterial activity was achieved against a few Gram‐positive strains and Gram‐negative strains of bacteria. This research activity can open a broad area of research towards textile dye degradation and antibacterial studies.