Divergence in the Expression of Molecular Markers of Neuronal Activation in the Parvocellular Paraventricular Nucleus of the Hypothalamus Evoked by Alcohol Administration via Different Routes

Abstract

Immediate early gene (IEG) expression has been routinely used by neuroscientists as an index of neuronal activation. In the case of the hypothalamic-pituitary-adrenal axis, induction of c-fos and/or NGFI-B mRNAs in the parvocellular paraventricular nucleus (pPVN) has been documented after a variety of stimuli that increase adrenocorticotropin (ACTH) in the systemic circulation. However, the functional relationship between expression of IEGs and transcription of the genes for the ACTH secretagogues corticotropin-releasing factor (CRF) and arginine vasopressin (AVP) is not clear. While investigating the neuroendocrine correlates of alcohol administration via different routes (intraperitoneal vs intragastric), we noted a difference in the time course of NGFI-B mRNA expression in the pPVN, despite comparable dynamics in ACTH secretion. By comparing the temporal cascade of transcriptional events in vivo after alcohol injection via either route, we sought to determine functional relationships between IEGs and the induction of CRF and AVP heteronuclear RNAs (hnRNAs). One advantage of our paradigm is the use of the same stimulus (systemic alcohol injection) in which access to the CNS does not differ between the groups to be compared. Intraperitoneal administration of the drug resulted in significant increases in c-fos mRNA, Fos protein, CRF hnRNA, and AVP hnRNA. In contrast, intragastric treatment evoked a brief, modest elevation in c-fos mRNA and Fos protein, increased AVP hnRNA, and caused no detectable change in CRF hnRNA. These data indicate that robust increases in CRF hnRNA are closely linked to full expression of c-fos mRNA and Fos protein. In addition, the expression of NGFI-B after both routes of administration is indicative of cellular activation within the pPVN in parallel with secretion of ACTH.