Central histaminergic involvement during stress in rats

Area of Science:

• Neuropharmacology
• Stress Physiology
• Immunology

Background:

• Restraint stress (RS) is a significant physiological challenge, inducing gastric ulcerogenesis, elevated corticosterone, and altered immune responses.
• The role of central histaminergic (HA) transmission in mediating these stress-induced effects remains incompletely understood.

Purpose of the Study:

• To investigate the involvement of central HA pathways in restraint stress (RS)-induced gastric ulcerogenesis, corticosterone release, and immune responses in rats.
• To evaluate the effects of drugs modulating HA transmission on these stress markers.

Main Methods:

• Rats were subjected to various restraint stress (RS) protocols, including prolonged exposure and cold stress (CRS).
• Drugs evaluated included a neuronal HA depletor (alpha-FMH), a mast cell degranulator (C-48/80), an H1-blocker (pheniramine), and an H2-blocker (zolantidine).
• Gastric mucosal erosions, plasma corticosterone levels, and humoral immune responses (in SRBC-immunized rats) were assessed.

Main Results:

• RS protocols consistently induced gastric lesions and elevated corticosterone levels.
• Alpha-FMH, C-48/80, and pheniramine significantly attenuated stress-induced gastric damage and corticosterone elevation.
• Pheniramine, but not zolantidine, also reversed the RS-induced suppression of humoral immune responses.

Conclusions:

• Central histaminergic (HA) pathways play a crucial role in mediating visceral, endocrinal, and immune responses to restraint stress (RS).
• Both neuronal and extraneuronal (mast cell) HA, acting via H1-receptors, are implicated in these stress-related effects.