Abstract
(1) Background: Negative experiences during adolescence increase the vulnerability to develop mental disorders later in life. A better understanding of the mechanisms underlying these long-term alterations could help to identify better therapeutic interventions. (2) Methods: Adolescent male Wistar rats were used to explore the effects of repeated stress and alcohol exposure on anxiety-like behaviors, plasma corticosterone levels and the gene expression of the endocannabinoid system (ECS) and other relevant signaling systems (glutamatergic, corticotropin-releasing hormone (CRH) and neuropeptide Y (NPY)) in the amygdala and the medial prefrontal cortex (mPFC). (3) Results: Overall, both stress and alcohol induced anxiety-like behaviors, but only the alcohol-exposed rats displayed increased plasma levels of corticosterone. In the amygdala, there was a general deficit in the gene expression of the ECS and increases in the mRNA levels of certain subunits of glutamate receptors. Interestingly, there were significant interaction effects between stress and alcohol on the expression of the NMDA receptor subunits. In addition, increased mRNA levels of the CRH receptor were observed in alcohol-exposed rats. In the mPFC, alcohol exposure was associated with an increase in the gene expression of the ECS. By contrast, the combination of stress and alcohol produced opposite effects. (4) Conclusions: In summary, early stress and alcohol exposure induced long-term anxiety-like behavior in male rats but different mechanisms are involved in these maladaptive changes in the brain.
Highlights
We have reported that both acute restraint stress and alcohol exposure during adolescence result in an increased anxiety-like behavior and high plasma levels of corticosterone in young adult male rats, but this anxious phenotype is associated with different mechanisms in the amygdala [31]
We evaluated the anxiety-like behavior, plasma corticosterone levels and gene expression of signaling systems in the amygdala and the medial prefrontal cortex (mPFC) of young male adult rats (PND77) exposed to five consecutive episodes of restraint stress and 4 weeks of intermittent alcohol during adolescence
We evaluated the effects of repeated restraint stress and/or intermittent alcohol exposure during adolescence on the mRNA expression of some receptors involved in the glutamatergic signaling in the amygdala
Summary
Adolescence is a crucial developmental period during the transition from childhood to adulthood. During this period of maturation, many morphological and functional changes occur, which make the adolescent brain highly vulnerable to the impact of stressful events in neuronal circuitry. Repeated life stress is considered as one of the major environmental risk factors that increases vulnerability to later psychiatric disorders [1]. When stress is experienced during adolescence, it produces enduring effects on behavior, including an increased susceptibility to an early onset of problem drinking and Biomedicines 2022, 10, 593.
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