ROLE OF ARGININE-VASOPRESSIN AND CORTICOTROPIN-RELEASING FACTOR IN MEDIATING ALCOHOL-INDUCED ADRENOCORTICOTROPIN AND VASOPRESSIN SECRETION IN MALE-RATS BEARING LESIONS OF THE PARAVENTRICULAR NUCLEI

In male rats, lesions of the paraventricular nucleus (PVN) of the hypo thalamus attenuate, but do not abolish, adrenocorticotropin (ACTH) sec retion in response to acute alcohol injection. As the PVN is the major source of corticotropin-releasing factor (CRF) in the median eminence , this observation suggests that extra-PVN brain regions, and/or ACTH secretagogues other than CRF (e.g. arginine vasopressin (AVP)), mediat e ACTH stimulation by alcohol. This hypothesis was tested by examining the effect of AVP immunoneutralization in PVN-lesioned (PVNx) rats. R emoval of endogenous AVP diminished alcohol-evoked ACTH secretion in b oth sham-operated and PVNx animals, indicating that AVP from outside t he PVN partially mediates the hypothalamic-pituitary-adrenal (HPA) axi s response to alcohol. This led us to determine whether alcohol might also regulate AVP steady-state gene expression in the supraoptic nucle us (SON) and PVN, and/or CRF mRNA in the PVN and the central nucleus o f the amygdala (AMY). In the magnocellular portion of the PVN, sham-op erated animals showed significantly increased PVN levels of both CRF a nd AVP mRNAs 3 h after alcohol. In the SON, alcohol administration ten ded to decrease AVP gene expression in PVNx rats, while the drug incre ased AVP mRNA levels in the SON of sham-operated rats. AMY levels of C RF mRNA were unaffected by these manipulations. Finally, since the reg ulation of alcohol-induced AVP mRNA. levels in the SON appeared to dep end on the presence of the PVN, we measured peripheral levels of AVP i n both sham-operated and PVNx animals after injection of vehicle or al cohol. Although AVP decreased in all groups, alcohol depressed AVP sec retion to a greater extent in PVNx animals, suggesting that AVP system s are more sensitive to inhibition in the absence of the PVN. Our resu lts demonstrate that although AVP of PVN origin may participate in reg ulating the stimulatory effect to AVP on ACTH secretion, AVP from area s other than the PVN also plays a role. Additionally, regulation of bo th AVP gene expression in the SON and secretion in the systemic circul ation are altered in rats bearing lesions of the PVN.