Background: Alcohol use disorder is underdiagnosed and undertreated, and up to 50% of alcohol-abstinent patients diagnosed with alcohol dependence relapse within the first year of treatment. Current treatments for the maintenance of alcohol abstinence in patients with alcohol use disorder have limited efficacy, and there is an urgent need for novel treatment strategies. Decreased cerebral glucose metabolism and increased brain uptake of acetate were recently reported in heavy drinkers, relative to controls.
View Article and Find Full Text PDFOne of the major histopathological hallmarks of Alzheimer's disease (AD) is cerebral deposits of extracellular β-amyloid peptides. Preclinical studies have pointed to glucagon-like peptide 1 (GLP-1) receptors as a potential novel target in the treatment of AD. GLP-1 receptor agonists, including exendin-4 and liraglutide, have been shown to promote plaque-lowering and mnemonic effects of in a number of experimental models of AD.
View Article and Find Full Text PDFThe few available data on the pharmacological effect of 5-HT5A receptors suggest that antagonists may have anxiolytic, antidepressant and antipsychotic activity. The aim of our study was to verify these suggestions in relevant animal models. Two 5-HT5A antagonist ligands, SB-699551-A (N-[2-(dimethylamino)ethyl]-N-[[4'-[[(2-phenylethyl)amino]methyl][1,1'-biphenyl]-4-yl]methyl]cyclopentanepropanamide dihydrochloride) (3-60 mg/kg, intraperitoneally) and A-843277 (N-(2,6-dimethoxybenzyl)-N'[4-(4-fluorophenyl)thiazol-2-yl]guanidine) (3-30 mg/kg, intraperitoneally), were examined in the open-field test, in a foot-shock-induced ultrasonic vocalization test, in the forced swim test (FST) and in the amphetamine-induced and phencyclidine-induced hyperlocomotion tests to examine their effect on general behavioural patterns, and their anxiolytic-like, antidepressant-like and antipsychotic-like properties, respectively.
View Article and Find Full Text PDFMetabotropic glutamate receptors of the subtype 5 (mGluR(5)) are located in brain regions implicated in schizophrenia such as the cerebral cortex or the nucleus accumbens. They may therefore provide an interesting target for the treatment of psychoses. Currently available agonists of mGluR(5) are not selective, do not penetrate the brain and induce a tonic activation resulting in a rapid desensitization.
View Article and Find Full Text PDFRecently, it has been proposed that activation of either metabotropic glutamate receptors e.g. mGlu(5) by positive allosteric modulators or stimulation of mGluR(2/3) receptors by agonists may offer new strategy in schizophrenia treatment.
View Article and Find Full Text PDFIt has been proposed that activation of metabotropic glutamate receptor subtype 2/3 (mGluR2/3) may induce both antipsychotic and anxiolytic effects. The aim of this study was to evaluate further the effect of the mGluR2/3 agonist, LY354740 [(+)-2-aminobicyclo(3.1.
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