AKB48 is a designer drug belonging to the indazole synthetic cannabinoids class, illegally sold as herbal blend, incense, or research chemicals for their psychoactive cannabis-like effects. In the present study, we investigated the pharmacological and behavioral effects of AKB48 in male rats and measured the pharmacodynamic effects of AKB48 and simultaneously determined its plasma pharmacokinetic. AKB48 at low doses preferentially stimulated dopamine release in the nucleus accumbens shell (0.25 mg/kg) and impaired visual sensorimotor responses (0.3 mg/kg) without affecting acoustic and tactile reflexes, which are reduced only to the highest dose tested (3 mg/kg). Increasing doses (0.5 mg/kg) of AKB48 impaired place preference and induced hypolocomotion in rats. At the highest dose (3 mg/kg), AKB48 induced hypothermia, analgesia, and catalepsy; inhibited the startle/pre-pulse inhibition test; and caused cardiorespiratory changes characterized by bradycardia and mild bradipnea and SpO2 reduction. All behavioral and neurochemical effects were fully prevented by the selective CB receptor antagonist/inverse agonist AM251. AKB48 plasma concentrations rose linearly with increasing dose and were correlated with changes in the somatosensory, hypothermic, analgesic, and cataleptic responses in rats. For the first time, this study shows the pharmacological and behavioral effects of AKB48 in rats, correlating them to the plasma levels of the synthetic cannabinoid. AKB48 (PubChem CID: 57404063); AM251 (PubChem CID: 2125).
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http://dx.doi.org/10.3389/fnins.2019.01163 | DOI Listing |
Mol Biol Evol
January 2025
Shmunis School of Biomedicine and Cancer Research, George S Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel.
Bats have adapted to pathogens through diverse mechanisms, including increased resistance - rapid pathogen elimination, and tolerance - limiting tissue damage following infection. In the Egyptian fruit bat (an important model in comparative immunology) several mechanisms conferring disease tolerance were discovered, but mechanisms underpinning resistance remain poorly understood. Previous studies on other species suggested that elevated basal expression of innate immune genes may lead to increased resistance to infection.
View Article and Find Full Text PDFInflammation
January 2025
Department of Chemistry, University of Agriculture Faisalabad, Faisalabad, Pakistan.
Parkinson's disease (PD) stands as the sec most prevalent incapacitating neurodegenerative disorder characterized by deterioration of dopamine-producing neurons in the substantia nigra. Coenzyme Q10 (CoQ10) has garnered attention as a potential antioxidant, anti-inflammatory agent and enhancer of mitochondrial complex-I activity. This study aimed to examine and compare the effectiveness of liposomal and non-encapsulated CoQ10 in rotenone induced-PD mouse model over a 21-day treatment duration.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Department of Pathology, University of California San Diego, La Jolla, CA 92093.
We hypothesized that a strategy employing tissue-specific endothelial cells (EC) might facilitate the identification of tissue- or organ-specific vascular functions of ubiquitous metabolites. An unbiased approach was employed to identify water-soluble small molecules with mitogenic activity on choroidal EC. We identified adenosine diphosphate (ADP) as a candidate, following biochemical purification from mouse EL4 lymphoma extracts.
View Article and Find Full Text PDFSwiss Med Wkly
November 2024
Department of Medicine, University of California at San Francisco, San Francisco, CA, USA.
Cigarette smoking remains an enormous public health problem causing millions of preventable deaths annually worldwide. Although safe and efficient smoking cessation pharmacotherapies such as nicotine replacement products and the medications varenicline and bupropion are available, long-term abstinence rates remain low and new approaches to help smokers successfully quit smoking are needed. In recent years, electronic nicotine delivery systems such as e-cigarettes and heated-tobacco products, and novel smokeless nicotine delivery products like nicotine pouches have gained widespread popularity.
View Article and Find Full Text PDFAging Ment Health
January 2025
Institute for Applied Social Sciences, Cener Health, Music Therapy Lab, Technical University of Applied Social Sciences Würzburg-Schweinfurt, Würzburg, Germany.
Objectives: Due to the limited effectiveness of pharmacological treatment, there is a growing need to explore non-pharmacological psychosocial interventions such as music therapy when treating the behavioural and psychological symptoms of dementia (BPSD).
Method: We randomised 57 nursing home residents into individual active music therapy plus standard care (aMT), individual receptive music therapy with tactile sound vibration plus standard care (rMT), or the standard care control group (CG). A trained music therapist provided 12 sessions over 6 weeks.
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