Acute stress and alcohol exposure during adolescence result in an anxious phenotype in adulthood: Role of altered glutamate/endocannabinoid transmission mechanisms

内大麻素系统 大麻素受体 内分泌学 内科学 单酰甘油脂肪酶 谷氨酸受体 大麻素 皮质酮 扁桃形结构 受体 杏仁核 焦虑症 化学 心理学 医学 激素 抗焦虑药 兴奋剂
作者
Laura Sánchez‐Marín,María Flores-López,Antoni Pastor,Ana Gavito,Juan Suárez,Rafael de la Torre,Francisco Javier Pavón,Fernando Rodrı́guez de Fonseca,Antonia Serrano
出处
期刊:Progress in Neuro-psychopharmacology & Biological Psychiatry [Elsevier BV]
卷期号:113: 110460-110460 被引量:19
标识
DOI:10.1016/j.pnpbp.2021.110460
摘要

Stressful episodes and high alcohol consumption during adolescence are considered major risk factors for the development of psychiatric disorders in adulthood. Identification of mechanisms underlying these early events, which enhanced vulnerability to mental illness, is essential for both their prevention and treatment.Male Wistar rats were used to investigate the long-term effects of early restraint stress and intermittent alcohol exposure (intragastric administration of 3 g/kg ethanol; 4 days/week for 4 weeks during adolescence) on anxiety-like behavior and the expression of signaling systems associated with emotional behaviors [e.g., corticosterone, fatty acid-derived molecules and endocannabinoid enzymes, glutamate receptor subunits, corticotropin releasing hormone receptors (CRHR1 and CRHR2) and neuropeptide Y receptors (NPY1R and NPYR2)] in the blood and amygdala.Overall, both stress and alcohol exposure during adolescence induced anxiogenic-like behaviors, increased plasma levels of corticosterone and increases in the amygdalar expression of the cannabinoid CB2 receptor and certain subunits of glutamate receptors (i.e., mGluR1, mGluR5 and NMDAR1) in young adult rats. In addition, there were specific main effects of alcohol exposure on the expression of the cannabinoid CB1 receptor, monoacylglycerol lipase (MAGL) and NPY2R in the amygdala, and significant increases were observed in rats exposed to alcohol. Interestingly, there were significant interaction effects between restraint stress and alcohol exposure on the expression of plasma 2-arachidonoyl glycerol (2-AG), and both CRHR1,2 and NPY1R in the amygdala. Thus, the restraint stress was associated with increased 2-AG levels, which was not observed in rats exposed to alcohol. The alcohol exposure was associated with an increased expression of CRHR1,2 but the restraint stress prevented these increases (stress alcohol rats). In contrast, NPY1R was only increased in rats exposed to stress and alcohol. Finally, we did not observe any potentiation of the behavioral and molecular effects by the combination of stress and alcohol, which is concordant with an overall ceiling effect on some of the variables.Separate and combined early stress and alcohol induced a common anxious phenotype with increased corticosterone in adulthood. However, there were differences in the amygdalar expression of signaling systems involved in maladaptive changes in emotional behavior. Therefore, our results suggest the existence of partially different mechanisms for stress and alcohol exposures.
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