Chronic exposure to antibodies directed against anti-opiate peptides alter δ-opioid receptor levels

The development of addictive states in response to chronic opioid use may be regulated partially by the release of endogenous peptides. These anti-opiate peptides (AOP) are secreted or released into the CNS and produce diverse actions that counterbalance the effects of prolonged opiate exposure. Though the mechanism(s) by which these peptides exert their physiological properties remain largely unknown, there is some indication that AOP’s modulate opioid receptor levels. In this study, we investigated the effects of chronically infused α-melanocyte stimulating hormone (α-MSH), dynorphin_1-8 (DYN_1-8), dynorphin A (DYNA), and NPFF antibodies on δ-opioid receptor expression in rat brains. Quantitative autoradiographic experiments revealed that antibodies directed against α-MSH and DYNA produced significant increases in delta receptor levels in the caudate, claustrum, and cingulate cortex of the rat brain. Conversely, NPFF monoclonal antibodies caused significant decreases in the caudate, nucleus accumbens, olfactory tubercle, and cingulate cortex. These results suggest that the density of δ-opioid receptors is affected by changes in the levels of the anti-opioid peptides in the extracelluar fluid in the rat brain.