Background
Exposure to negative experiences during adolescence increases susceptibility to mental disorders in adulthood. These risks vary significantly between sexes, with males and females potentially experiencing different impacts. Identifying the mechanisms underlying these early events and understanding their sex-specific effects are essential for both prevention and treatment strategies.
Methods
Adolescent Wistar rats of both sexes were used to explore the long-term effects of acute restraint stress and alcohol exposure on the hypothalamic-pituitary-adrenal (HPA) axis activity and the mRNA levels of the ACTH precursor proopiomelanocortin (POMC), the glucocorticoid receptor (GR), the mineralocorticoid receptor (MR), and several signaling systems, including the corticotropin releasing hormone (CRH), the neuropeptide Y (NPY), the opioid receptors (OPRs), and the arginine vasopressin (AVP) systems in the amygdala and hypothalamus.
Results
In males, our findings revealed: 1) stress increased plasma corticosterone (CORT) levels; 2) stress and/or alcohol upregulated CRF signaling; 3) stress or alcohol decreased amygdalar NPY signalling, but increased it in the hypothalamus, increase mitigated by combined exposure; 4) alcohol elevated POMC and MR expression, attenuated by stress and alcohol combination; 5) stress and/or alcohol decreased mRNA levels of opioid receptors; 6) stress and/or alcohol upregulated Avp mRNA levels, but downregulated its receptor expression. In females, our findings revealed: 1) stressed rats showed elevated plasma ACTH levels, and both stress and alcohol increased CORT levels, but combined exposure dampened this rise; 2) alcohol increased amygdalar Crh mRNA, while stress reduced hypothalamic Crh mRNA and alcohol downregulated its receptors; 3) combined stress and alcohol significantly increased amygdalar NPY system mRNA, but downregulated it in the hypothalamus; 4) alcohol decreased POMC and GR expression; 5) alcohol increased Oprm1 and Oprs1 mRNA levels, while stress reduced Oprd1 expression; 6) stress and/or alcohol upregulated Avpr1a mRNA, with the combination increasing Avp mRNA.
Conclusions
This study demonstrated that both acute restraint stress and alcohol exposure during adolescence induced long-term, sex-dependent alterations in the mRNA expression of several system involved in the regulation of the stress response and reward. This highlights the importance of considering sex differences in developing strategies for the prevention and treatment of stress-related disorders.
