A, the firing rate (averaged in consecutive 10 s intervals) of a single oxytocin cell recorded from a morphine-naïve rat administered CCK (20 μg kg−1, i.v.) at 10, 30, 55 and 80 min, naloxone (NLX, 5 mg kg−1, i.v.) at 20 min and infused i.c.v. with benoxathian at 1.6 μg min−1 (Ben 1.6) from 40 to 70 min and at 5.3 μg min−1 (Ben 5.3) from 70 to 85 min. Benoxathian inhibited spontaneous activity and attenuated the response to CCK. B, the firing rate (averaged in consecutive 10 s intervals) of a single oxytocin cell recorded from a morphine-dependent rat administered CCK (20 μg kg−1, i.v.) at 10 min, naloxone (NLX, 5 mg kg−1, i.v.) at 30 min and infused i.c.v. with benoxathian (Ben; 5.3 μg min−1) from 20 to 35 and 65 to 95 min. The first infusion of benoxathian delayed the peak sustained increase in firing rate after naloxone and a second infusion later reversibly inhibited the withdrawal excitation. C, effects of benoxathian on subsequent withdrawal excitation of oxytocin neurones. The composite change in firing rate of oxytocin neurones was induced by naloxone (NLX; 5 mg kg−1, i.v. at t = 10 min) in morphine-dependent rats during i.c.v. infusion of benoxathian (Ben; 5.3 μg min−1, n = 7, ^) or vehicle (Veh, n = 6, •). The change in firing rate was calculated for each cell by subtracting the initial mean basal firing rate (measured over 5 min in 1 min bins) from the firing rate measured in each minute, and was expressed as a percentage (mean ±s.e.m.) of the maximum change observed for each cell. The magnitude of withdrawal excitation was significantly lower in the first 5 min after naloxone in the benoxathian-infused group than in the vehicle-infused group (P < 0.05, two-way RM ANOVA followed by Student-Newman-Keuls analyses). In vehicle-infused rats, the naloxone-induced increase in firing rate was maximal within 5 min. In contrast, in benoxathian-infused rats the maximum firing rate was not attained until 30–35 min after naloxone, 25–30 min after the end of the benoxathian infusion (P < 0.05 compared with the 5 min immediately following naloxone administration to i.c.v. benoxathian-infused rats).