Alcohol, stress hormones, and the prefrontal cortex: A proposed pathway to the dark side of addiction

Summary & key facts

This review paper brings together animal and human studies to explain how alcohol and stress hormones may change the prefrontal cortex and the body’s stress system as drinking moves from casual use toward dependence. The authors say alcohol raises stress hormones (glucocorticoids) right away, and repeated heavy use can produce lasting changes in the hypothalamic–pituitary–adrenal (HPA) axis and in prefrontal brain circuits. They propose a pathway in which these hormone-driven brain changes lead to a weaker HPA response (a “dampened” stress system) and stronger prefrontal inhibition of the stress center, which the authors suggest could increase relapse risk and help drive a spiral into depend

Key facts:

• The authors define a ‘‘binge’’ level as 0.08 g/dL blood alcohol; in their rodent model descriptions, alcohol levels stay below this in the Use phase but exceed it in the Abuse and Dependence phases.
• Alcohol acutely increases glucocorticoids (stress hormones); in rodent vapor models the paper notes corticosterone levels rose to values ‘‘far exceeding’’ the normal daily rhythm during alcohol exposure.
• Repeated heavy alcohol exposure in animals leads to neuroendocrine tolerance: animals show a weaker HPA (hypothalamic–pituitary–adrenal) response to alcohol over time. The paper reports this dampened response depends on prior alcohol exposu
• In the reviewed rodent data, dependent animals had lower CRF (corticotropin-releasing factor) mRNA in the hypothalamus than alcohol-naïve controls, with non-dependent animals showing intermediate levels.
• A CRF challenge (0.3 µg/kg, IV) produced a lower ACTH (adrenocorticotropic hormone) response in drinking rats compared with alcohol-naïve rats; non-dependent and dependent groups did not differ from each other on that test.
• The authors report that high glucocorticoid levels during heavy alcohol periods are associated with lower glucocorticoid receptor (GR) levels in the brain, and they cite evidence and prior work proposing increased local glucocorticoid produ
• Most of the specific mechanistic evidence summarized in the review comes from preclinical (rodent) studies, and the paper frames the changes in prefrontal circuitry and HPA function as a proposed pathway that requires more testing in humans

Topics

Neuroendocrine regulation and behavior Stress Responses and Cortisol Tryptophan and brain disorders

Categories

Behavioral Neuroscience Life Sciences Neuroscience

Tags

Addiction Alcohol Biochemistry Biology Cognition Effects of stress on memory Endocrinology Hippocampus Hormone Internal medicine Medicine Memory consolidation Neuroplasticity Neuroscience Prefrontal cortex Psychology