Quaternary naltrexone reveals the central mediation of conditional opioid analgesia

Earlier research has demonstrated that when rats are placed in a context associated with mild electric shock (1 mA/0.75 sec), environmental cues alone can produce conditional analgesia that suppresses pain sensitivity on the formalin test. This analgesia appears to be mediated by endogenous opioids since it is reversed by the centrally active opioid antagonists naloxone and naltrexone. Two experiments attempted to determine if peripheral or central opioids mediate this analgesia by employing quaternary naltrexone (QNTX), an antagonist which does not readily penetrate the blood-brain barrier at moderate doses. Intracerebroventricularly administered QNTX (10 micrograms) significantly reversed conditional analgesia, whereas intraperitoneally injected QNTX did not affect formalin-induced behavior. These results suggest that the conditional analgesia produced by our procedures is mediated by central, not peripheral, opioid mechanism(s).