The type 1 corticotropin-releasing factor (CRF<sub>1</sub>) receptor has received much attention for its putative role in the progression to alcohol dependence, although at present its success in clinical trials has been limited.
In the present randomized, double blind, placebo-controlled, triple-dummy crossover study, we juxtaposed a centrally-acting, citalopram (2 mg/unit BMI) neuroendocrine stimulation test with a peripherally-acting, dexamethasone (Dex) (1.5 mg)/corticotropin-releasing factor (CRF) (1 μg/kg) test in euthymic women (N = 38) and men (N = 44) with (54%) and without histories of alcohol dependence to determine whether sex, alcohol dependence or both influenced the adrenocorticotropic hormone (ACTH) and cortisol responses to the pharmacological challenges and to identify the loci of these effects.
Decades of research have described the importance of corticotropin-releasing factor (CRF) signaling in alcohol addiction, as well as in commonly co-expressed neuropsychiatric diseases, including anxiety and mood disorders.
Collectively our data show that CRF primarily acts at presynaptic CRF<sub>1</sub> to produce opposite effects on CeA evoked and spontaneous glutamate release and that the CRF system modulates CeA glutamatergic synapses throughout the development of alcohol dependence.
Recent work has also identified an important role for the CeA corticotropin-releasing factor (CRF) system in the interaction between anxiety/stress and alcohol dependence.
These findings are consistent with the hypothesized role of the extra hypothalamic corticotropin-releasing factor system dysregulation in the initiation and maintenance of alcoholism.
These findings are consistent with the hypothesized role of the extra hypothalamic corticotropin-releasing factor system dysregulation in the initiation and maintenance of alcoholism.
Alcohol dependence is associated with increased corticotropin releasing factor (CRF) influence on CeA GABA release and CRF type 1 receptor (CRF(1)) antagonists prevent the excessive alcohol consumption associated with dependence.
For example, genetic variations in pathways using the brain signaling molecule (i.e., neurotransmitter) dopamine, which likely mediate alcohol's rewarding effects, and in two hormonal systems involved in the stress response (i.e., the hypothalamic-pituitary-adrenal axis and the corticotropin-releasing factor system) affect alcoholism risk.
For example, genetic variations in pathways using the brain signaling molecule (i.e., neurotransmitter) dopamine, which likely mediate alcohol's rewarding effects, and in two hormonal systems involved in the stress response (i.e., the hypothalamic-pituitary-adrenal axis and the corticotropin-releasing factor system) affect alcoholism risk.
No association of CRH1 receptor polymorphism haplotypes, harm avoidance and other personality dimensions in alcohol dependence: results from the Munich gene bank project for alcoholism.