Increased opioid efficacy for inhibition of adenylyl cyclase in rat brain and 7315c cell membranes induced by chronic naltrexone treatment

Abstract

Long term administration of the opioid antagonist naltrexone results in an increase in μ-opioid receptor density in brain (1,2). Chronic naltrexone treatment also produces an increase in the analgesic potency of morphine (3) and this may be related to the increase in opioid receptors. It is unknown, however, whether the upregulation of the μ-opioid receptor following naltrexone treatment results in an enhanced regulation of second messenger systems by opioid agonists. In the current study, the effects of chronic naltrexone have been examined on the ability of μ-opioid receptors on brain membranes and on a non-neuronal tissue, the transplantable 7315c tumor cell that expresses μ- but not δ- or κ- opioid receptors (4,5), to bind [ 3 H]DAMGO and to respond to μ-opioid agonists and GTPγS in an adenylyl cyclase assay