Table 1.
PACAP in Stress-related Structures and Circuits
| BNST | |
| PACAP and PAC1R transcripts are densely expressed at high levels in the BNST | (Hannibal, 2002; Hashimoto et al., 1996; Joo et al., 2004) |
| BNST PACAP and PAC1R transcripts are upregulated following CVS | (Hammack et al., 2009) |
| BNST PACAP and PAC1R transcripts are upregulated by chronic E2 treatment in OVX females | (Ressler et al., 2011) |
| Anxiety-like behaviors in the open-field, EPM, and acoustic startle paradigms are increased by intra-BNST PACAP infusion | (Hammack et al., 2009; King et al., 2017; Roman et al., 2014) |
| Circulating plasma corticosterone and release is increased by intra-BNST PACAP infusion | (Lezak et al., 2014; Roman et al., 2014) |
| Chronic stress effects on behavioral and endocrine responses are blocked by intra-BNST PAC1R antagonism | (Roman et al., 2014) |
| BNST of male rats is sensitized to subsequent PACAP release and signaling following CVS | (King et al., 2017) |
| c-Fos activation in the BNST is blunted in PACAP KO mice | (Gaszner et al., 2012) |
| HPA axis | |
| PACAP and PAC1R transcripts are expressed endogenously in the PVN | (Condro et al., 2016; Hannibal, 2002; Hashimoto et al., 1996; Joo et al., 2004) |
| PVN PACAP transcripts are upregulated by CVS | (Hammack et al., 2009) |
| PVN PACAP expression is mediated by estrous cycle and is correlated with gonadotropin synthesis and secretion | (Moore et al., 2005) |
| c-Fos and vasopressin are elevated in the PVN by central PACAP infusion | (Meloni et al., 2016; Nomura et al., 1999) |
| PACAPergic projections form synapses with PVN CRH neurons | (Legradi et al., 1998) |
| CRH expression, production and secretion in the PVN is stimulated by PACAP | (Agarwal et al., 2005; Hashimoto et al., 2010) |
| PVN CRH levels are attenuated and stress-induced corticosterone release is impaired in PACAP KO mice | (Stroth & Eiden, 2010) |
| Corticosterone levels are increased by ICV PACAP | (Agarwal et al., 2005; Meloni et al., 2016) |
| Amygdala | |
| CeA | |
| PACAP (dense fiber staining) is expressed at high levels in CeA | (Condro et al., 2016; Hannibal, 2002; Hashimoto et al., 1996; Joo et al., 2004; Missig et al., 2014) |
| CeA PACAP and PAC1R expression is not upregulated by CVS | (Hammack et al., 2009) |
| Fear-like avoidant behaviors and anxiety-like behaviors are increased by intra-CeA PACAP infusion | (Legradi et al., 2007; Missig et al., 2014) |
| Intra-CeA PACAP effects on fear/anxiety are likely mediated via VPACRs (not PAC1Rs) | (Cho et al., 2012) |
| c-Fos is increased in the CeA following ICV PACAP | (Meloni et al., 2016) |
| CRH expression in the CeA is enhanced by ICV PACAP | (Dore et al., 2013) |
| BLA | |
| PAC1Rs and low levels of PACAP are expressed in the BLA | (Hannibal, 2002; Hashimoto et al., 1996; Joo et al., 2004) |
| PAC1R transcripts are upregulated following fear conditioning | (Andero et al., 2014) |
| BLA PACAP or PAC1R expression is not upregulated by CVS | (Hammack et al., 2009) |
| ANS | |
| PACAP is expressed in autonomic sensory areas | (Kormos & Gaszner, 2013) |
| Sympathetic outflow is stimulated by PACAP | (Tanida et al., 2010) |
| Epinephrine secretion is stimulated by PACAP, and compensatory catecholamine synthesis is enhanced by PACAP during prolonged stress to sustain epinephrine secretion | (Stroth & Eiden, 2010; Watanabe et al., 1992) |
| PACAP is involved in peripheral homeostatic balance under conditions of stress | (Tanida et al., 2010) |
| PACAP is expressed at higher levels in the adrenals of males under basal conditions | (Mosca et al., 2015) |
| Hippocampus | |
| PACAP and PAC1Rs are expressed throughout the hippocampal formation, including entorhinal cortex, CA1, CA2, CA3, and DG. | (Condro et al., 2016; Hannibal, 2002; Hashimoto et al., 1996; Joo et al., 2004; Kozicz et al., 1997; Otto et al., 1998; Vaudry et al., 2009) |
| PAC1R expression is primarily limited to mossy fibers in the hippocampus | (Otto et al., 2001) |
| PAC1Rs are expressed by newly proliferated NSCs in the SGZ | (Matsumoto et al., 2016) |
| Structural plasticity within the hippocampus is enhanced by PACAP (i.e., increased number of newly proliferated cells in the SVZ, SGZ and DG, and enhancesd neurite length, number, and increases soma size) | (Matsumoto et al., 2016; Mercer et al., 2004; Ogata et al., 2015; Ohta et al., 2006) |
| mPFC | |
| PACAP and PAC1Rs are expressed in the mPFC | (Condro et al., 2016; Hashimoto et al., 1996; Koves et al., 1991; Kozicz et al., 1997; Vaudry et al., 2009) |
| PAC1Rs are upregulated in the mPFC following fear conditioning | (Ressler et al., 2011) |
| PACAP transcripts are down regulated in the mPFC following CVS | (Makinson et al., 2015) |