As a neurotransmitter or neuromodulator, brain histamine has a variety of physiological roles in brain functions such as hypothalamic- pituitary- adrenal (HPA) activity. Histamine induces the release of ACTH through the activation of hypothalamic neurons containing vasopressin and CRH. Histamine induces the activity of HPA axis directly or indirectly. Endogenous opioids modulate the (HPA) axis ...