, 1999) and robust changes in eCB and NO levels in the hypothalamus (Di Marzo et al., 2001, Kirkham et al., 2002 and Squadrito et al., 1994). While we investigate GABA signaling in the DMH following

food deprivation, other studies have reported an increase in neuronal activity in the DMH, as assessed by changes in Fos expression, in response to refeeding following food deprivation (Johnstone et al., 2006 and Renner et al., 2010). Our finding that food deprivation produces an increase in GABA drive to DMH neurons is in agreement with these studies and suggests that enhanced inhibition of these neurons is a mechanism to cope with the lack of food. These neurons are then activated upon refeeding following a period of food

deprivation. Although we report LTPGABA of evoked synaptic GW-572016 mw responses this website following HFS in food-deprived animals, this is accompanied by a small decrease in the amplitude of spontaneous IPSCs. Under these conditions, in which CB1Rs are compromised, we surmise that HFS will still produce eCBs, but they have no presynaptic binding partner available. Thus, the eCBs may preferentially bind to postsynaptic TRPV channels and promote a postsynaptic LTDGABA. This putative postsynaptic LTD may rely on a mechanism similar to that reported at glutamate synapses in other brain regions (Chávez et al., 2010 and Grueter et al., 2010) and may explain why we observe a slight depression following HFS when both the CB1R and NO signaling pathways are blocked. Food deprivation is one of the most fundamental stressors to an organism, with elevated CORT levels observed within just 4 hr following removal of food from young rats (Dallman et al., 1999). In this study, we demonstrate that CORT, through actions at genomic glucocorticoid receptors, is essential for shifting the plasticity from LTDGABA to LTPGABA in the DMH following acute food deprivation. Accumulating evidence suggests that CORT can interfere with CB1R expression and signaling. In the PVN, we have recently reported a downregulation

of CB1Rs following repeated stress that is mediated by activation of genomic the glucocorticoid receptors (Wamsteeker et al., 2010). Prolonged CORT treatment also decreases the density of CB1Rs in the hippocampus (Hill et al., 2008) and impairs CB1R-mediated control of GABA transmission in the striatum (Rossi et al., 2008). Importantly, it appears that the increase in CORT must be robust and prolonged because challenges that cause either prolonged but small changes in CORT (social isolation) or robust but transient increases (30 min immobilization) failed to shift the balance of plasticity toward LTP. It is important to note that CORT can also induce eCB biosynthesis and release (Di et al., 2003, Hill et al., 2005 and Malcher-Lopes et al., 2006), and that elevated levels of eCBs can result in desensitization and synaptic exclusion of CB1Rs (Mikasova et al., 2008).