Luteinizing hormone secretion as a response to a second naltrexone administration

Previous studies with naltrexone (Nalt), a "long-lasting" opioid antagonist, demonstrated a rapid increase in luteinizing hormone (LH) secretion which gradually declined, reaching baseline values after 1 hr. A second Nalt challenge, 120 min later, caused only a blunted response. This poor reaction has been shown in this study not to be due to lack of pituitary responsiveness, because LH-releasing hormone treatment revealed a normal response. A time-response study was carried out in order to establish the refractory period length, by administering a second Nalt injection at 0 hr (immediately after the first injection) and at 2, 4, 8, 16, and 24 hr after the first bolus. Partial responsiveness could be achieved 2 and 4 hr after the first challenge. However, only after 8 hr was a full response recorded. The diurnal changes in serum LH (nadir at 18.00 hr) did not affect the response to Nalt challenge. It is suggested that in the presence of a Nalt blockade, nonopioid systems are able to "normalize" LH blood levels. However, when Nalt blood levels have fallen sufficiently to allow the endogenous opioid system to take primary control again, then a second Nalt injection will provoke a renewed response.