Heroin, morphine and other short-acting opiates regulate the activity of endogenous opioid systems, and chronic opiate exposure can cause a relative deficiency in beta-endorphin/mu opioid receptor system [7]. Although early studies reported a lack of effect on beta-endorphin-immunoreactivity levels in many brain regions of rodents [8], studies of pro-opiomelanocortin (POMC) gene expression indicated that chronic opiate exposure significantly decreased POMC mRNA levels in the hypothalamus [e.g., 17, 18]. Another interesting stress-related peptide is orexin: mu opioid receptor agonists (including beta-endorphin) inhibit orexin-producing neurons in the lateral hypothalamus [19]. Acute opiate withdrawal is associated with increased orexin expression and activity in this region [20, 21], which may play an important role in opiate-seeking behaviors [22, 23].
