Intranasal NPY also attenuated long-term changes in the GS-1101 ic50 central noradrenergic system induced by SPS, including the development of

increased sensitization of the LC to re-experiencing the forced swim (Serova et al., 2013). Taken together, PSS and SPS studies indicate that a single treatment with NPY near the time of the traumatic stress could provide long-lasting resilience to the development of PTSD and co-morbid impairments such as depression. Moreover, recent work also suggests that NPY may be efficacious as a treatment once PTSD-like symptoms have already manifested. Rats given IN NPY one week after SPS, when PTSD-like symptoms have manifested, exhibit anxiety-like behavior similar to unstressed controls up to 2 days later (Serova

et al., 2014). Rats administered NPY after SPS also had reduced depression-like behavior (Serova et al., 2014). Further studies are necessary to determine if intranasal NPY reverses other impairments associated with PTSD, as well as the duration and sustainability of the improvements. The examples presented herein demonstrate that pharmacological interventions targeting the NPY system display much promise for the treatment of numerous stress-related psychiatric disorders. Future pharmacotherapeutic studies should consider targeting the central NPY Selleck PLX-4720 system in stress-related emotionality and resilience. The preponderance of data suggests that NPY itself has significant therapeutic potential as a mediator of stress resilience. There are two major challenges associated with the development of NPY as a drug for psychiatric disorders; it is a peptide and it has a broad range of activities that may result in undesirable

side-effects. The attractiveness and challenges of peptide therapeutics for CNS disorders has recently been reviewed (McGonigle, 2012). Peptides do not accumulate in tissues and are effectively metabolized by endogenous enzymes; therefore they have limited potential for drug–drug interactions. Rutecarpine However, peptides have short half-lives and several methods have been introduced to prolong their stability in vivo. Encouragingly, as demonstrated in rodent models ( Serova and et al, 2013, Laukova and et al, in press and Serova and et al, 2014), NPY may confer long-lasting benefits for stress resilience despite its short half-life. Although this review has concentrated on the beneficial effects of NPY in the CNS, NPY also has multiple actions in the periphery (Hirsch and Zukowska, 2012, Held and et al, 2006 and Pedrazzini et al., 2003). For example, NPY is a co-transmitter in sympathetic nerves, plays a role in vascular tone, and contributes to cardiovascular remodeling (Zukowska-Grojec, 1995, Edvinsson and et al, 1984, Schuerch and et al, 1998 and Abe et al., 2007).