Lee Peyton1, Brandon Emanuel León2, Hesham Essa1, Yijuang Chern3, Doo-Sup Choi4,5. 1. Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN, 55905, USA. 2. Regenerative Sciences Program, Center for Regenerative Medicine, Mayo Clinic College of Medicine Rochester, Rochester, MN, 55905, USA. 3. Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan. 4. Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN, 55905, USA. choids@mayo.edu. 5. Department of Psychiatry and Psychology, Mayo Clinic College of Medicine Rochester, Rochester, MN, 55905, USA. choids@mayo.edu.
Abstract
RATIONALE: Withdrawal from chronic alcohol exposure produces various physical and mental withdrawal symptoms. Activation of adenosine receptors is known to inhibit withdrawal-induced excitation. However, limited studies investigate how adenosine analogs may prove helpful tools to alleviate alcohol withdrawal-related affective behaviors. OBJECTIVES: This study aimed to investigate the effects of J4 compared with saline using the mice vapor or voluntary ethanol drinking model on behavioral endpoints representing ethanol-withdrawal negative emotionality commonly observed during abstinence from chronic alcohol use. METHODS: We subjected C57BL/6 J mice to chronic intermittent ethanol (CIE) exposure schedule to investigate how 72-h withdrawal from alcohol alters affective-like behavior. Next, we determined how treatment with J4, a second-generation adenosine analog, influenced affective behaviors produced by alcohol withdrawal. Finally, we determined how J4 treatment alters voluntary ethanol drinking using the two-bottle-choice drinking paradigm. RESULTS: Our results show that 72-h withdrawal from chronic intermittent ethanol exposure produces limited affective-like disturbances in male C57BL/6 J mice exposed to 4 cycles ethanol vapor. Most importantly, J4 treatment irrespective of ethanol exposure decreases innate anxiety-like behavior in mice. CONCLUSIONS: Withdrawal from chronic intermittent ethanol exposure and subsequent behavioral testing 72 h later produces minimal affective-like behavior. J4 treatment did however reduce marble-burying behavior and increased time spent in open arms of the elevated plus maze, suggesting J4 may be useful as a general anxiolytic.
RATIONALE: Withdrawal from chronic alcohol exposure produces various physical and mental withdrawal symptoms. Activation of adenosine receptors is known to inhibit withdrawal-induced excitation. However, limited studies investigate how adenosine analogs may prove helpful tools to alleviate alcohol withdrawal-related affective behaviors. OBJECTIVES: This study aimed to investigate the effects of J4 compared with saline using the mice vapor or voluntary ethanol drinking model on behavioral endpoints representing ethanol-withdrawal negative emotionality commonly observed during abstinence from chronic alcohol use. METHODS: We subjected C57BL/6 J mice to chronic intermittent ethanol (CIE) exposure schedule to investigate how 72-h withdrawal from alcohol alters affective-like behavior. Next, we determined how treatment with J4, a second-generation adenosine analog, influenced affective behaviors produced by alcohol withdrawal. Finally, we determined how J4 treatment alters voluntary ethanol drinking using the two-bottle-choice drinking paradigm. RESULTS: Our results show that 72-h withdrawal from chronic intermittent ethanol exposure produces limited affective-like disturbances in male C57BL/6 J mice exposed to 4 cycles ethanol vapor. Most importantly, J4 treatment irrespective of ethanol exposure decreases innate anxiety-like behavior in mice. CONCLUSIONS: Withdrawal from chronic intermittent ethanol exposure and subsequent behavioral testing 72 h later produces minimal affective-like behavior. J4 treatment did however reduce marble-burying behavior and increased time spent in open arms of the elevated plus maze, suggesting J4 may be useful as a general anxiolytic.
Authors: Hyung W Nam; Sally R McIver; David J Hinton; Mahesh M Thakkar; Youssef Sari; Fiona E Parkinson; Phillip G Haydon; Doo-Sup Choi Journal: Alcohol Clin Exp Res Date: 2012-02-06 Impact factor: 3.455
Authors: A Cheffer; A R G Castillo; J Corrêa-Velloso; M C B Gonçalves; Y Naaldijk; I C Nascimento; G Burnstock; H Ulrich Journal: Mol Psychiatry Date: 2017-09-26 Impact factor: 15.992