Activation of the HPA axis and depression of feeding behavior induced by restraint stress are separately regulated by PACAPergic neurotransmission in the mouse

Abstract

We measured serum CORT elevation in wild-type and PACAP-deficient C57Bl/6N male mice after acute (1 hr) or prolonged (2–3 hr) daily restraint stress for seven days. The PACAP-dependence of CORT elevation was compared to that of stress-induced hypophagia. Daily restraint induced unhabituated peak CORT elevation, and hypophagia/weight loss, of similar magnitude for 1, 2 and 3 hr of daily restraint, in wild-type mice. Peak CORT elevation, and hypophagia, were both attenuated in PACAP-deficient mice for 2 and 3 hrs daily restraint. Hypophagia induced by 1-hr daily restraint was also greatly reduced in PACAP-deficient mice, however CORT elevation, both peak and during recovery from stress, was unaffected. Thus, hypothalamic PACAPergic neurotransmission appears to affect CRH gene transcription and peptide production, but not CRH release, in response to psychogenic stress. A single exposure to restraint sufficed to trigger hypophagia over the following 24 hours. PACAP deficiency attenuated HPA axis response (CORT elevation) to prolonged (3 hr) but not acute (1 hr) single-exposure restraint stress, while hypophagia induced by either a single 1 hr or a single 3 hr restraint were both abolished in PACAP-deficient mice. These results suggest that PACAP’s actions to promote suppression of food intake following an episode of psychogenic stress is unrelated to the release of CRH into the portal circulation to activate the pituitary-adrenal axis. Furthermore, demonstration of suppressed food intake after a single 1-hr restraint stress provides a convenient assay for investigating the location of the synapses and circuits mediating the effects of PACAP on the behavioral sequelae of psychogenic stress.

The Good, the Bad and the Unknown Aspects of Ghrelin in Stress Coping and Stress-Related Psychiatric Disorders

“…Also in subchronic and chronic stress paradigms food intake and body weight are typically negatively affected. For example, repeated immobilization stress decreased food intake (Jeong et al, 2013;Jiang and Eiden, 2016) and in parallel decreased (Li et al, 2015;Jiang and Eiden, 2016;Mograbi et al, 2020) or had no effect on body weight (Jeong et al, 2013). Also exposure to a flooded cage for five days decreased body weight (Ochi et al, 2008) and, similarly, social isolation for a week (Izadi et al, 2018) or chronic administration of foot shocks (Rostamkhani et al, 2016) reduced food intake and body weight.…”

Identification of a neurocircuit underlying regulation of feeding by stress-related emotional responses

“…Extensive studies on PVH projection patterns and circuit function suggest that PVH neurons regulate feeding through various projections to within the hypothalamus or downstream brain stem and hindbrain neurons 1,23–29 . Among various subtypes of PVH neurons, those expressing corticotrophin-releasing hormone (CRH neurons) are known to initiate the neuroendocrine aspect of stress responses; however, this response is not involved in stress-induced hypophagia 30,31 . It is not clear how PVH neurons integrate stress-related responses to feeding control.…”

Lessons from regular gathering of experts in stress research: focus on pathophysiological consequences of stress exposure

“…Numerous presentations noted the importance of prior stress experience in determining the impact of new stressors on sensitive outcomes, such as drug reinstatement (Hadad et al, 2016), highlighting the need to incorporate consideration of context in interpretation of the impact of stress on the brain. Another resonating theme was the ability of stress-effector molecules to coordinate a diversity of stress responses via independent mechanisms, e.g., different control mechanisms for body weight and HPA axis stress responses by pituitary adenylate cyclase activating polypeptide (PACAP) (Jiang & Eiden, 2016), parallel activation of anxiety, and emotional responses by vasopressin (Csikota et al, 2016). Moreover, presentations highlighted the emerging recognition of the importance of classical transmitter systems (GABA, glutamate) as key coordinators in the development of stress circuitry (Balaszfi et al, 2016).…”