An Update on CRF Mechanisms Underlying Alcohol Use Disorders and Dependence.
Alcohol is the most commonly used and abused substance worldwide. The emergence of alcohol use disorders, and alcohol dependence in particular, is accompanied by functional changes in brain reward and stress systems, which contribute to escalated alcohol drinking and seeking. Corticotropin-releasing factor (CRF) systems have been critically implied in the transition toward problematic alcohol drinking and alcohol dependence. This review will discuss how dysregulation of CRF function contributes to the vulnerability for escalated alcohol drinking and other consequences of alcohol consumption, based on preclinical evidence. CRF signaling, mostlyviaCRF1 receptors, seems to be particularly important in conditions of excessive alcohol taking and seeking, including during early and protracted withdrawal, relapse, as well as during withdrawal-induced anxiety and escalated aggression promoted by alcohol. Modulation of CRF1 function seems to exert a less prominent role over low to moderate alcohol intake, or to species-typical behaviors. While CRF mechanisms in the hypothalamic-pituitary-adrenal axis have some contribution to the neurobiology of alcohol abuse and dependence, a pivotal role for extra-hypothalamic CRF pathways, particularly in the extended amygdala, is well characterized. More recent studies further suggest a direct modulation of brain reward function by CRF signaling in the ventral tegmental area, nucleus accumbens, and the prefrontal cortex, among other structures. This review will further discuss a putative role for other components of the CRF system that contribute for the overall balance of CRF function in reward and stress pathways, including CRF2 receptors, CRF-binding protein, and urocortins, a family of CRF-related peptides.
Department of Psychobiology, Escola Paulista de Medicina, Universidade Federal de São Paulo , São Paulo, São Paulo , Brazil.
Isabel Marian Hartmann
IM
Quadros
Department of Psychobiology, Escola Paulista de Medicina, Universidade Federal de São Paulo , São Paulo, São Paulo , Brazil.
Giovana Camila
GC
Macedo
Department of Psychobiology, Escola Paulista de Medicina, Universidade Federal de São Paulo , São Paulo, São Paulo , Brazil.
Liz Paola
LP
Domingues
Department of Psychobiology, Escola Paulista de Medicina, Universidade Federal de São Paulo , São Paulo, São Paulo , Brazil.
Cristiane Aparecida
CA
Favoretto
addiction; alcohol; alcohol self-administration; alcohol-related aggression; animal models; mesocorticolimbic system; neuropeptides; sensitization