Figure 5.

MC4R in CeA and MOR in vlPAG modulate thermal nociception. A, Hindpaw withdrawal latencies of naive (white) and alcohol-dependent (red) rats following intra-CeA infusion of HS014. *p < 0.05 versus naive. ^#p < 0.05, effect of HS014. B, Hindpaw withdrawal latency of naive rats is significantly reduced following intra-CeA infusion of αMSH. *p < 0.05 versus control. C, Hindpaw withdrawal latencies of naive rats following intra-PAG infusion of DAMGO and intra-CeA infusion of 0.3 μg αMSH. Intra-PAG administration of DAMGO before αMSH prevents thermal hyperalgesia. *p < 0.05 versus 0 μg DAMGO. A–C, Top, Cannulae placement. D, IPSPs are evoked in putative PAG pyramidal neurons by nearby electrical stimulation (left). Superthreshold current injection evoked action potentials (APs) under baseline conditions (middle), but APs are blocked by concurrent stimulation of local inhibition (right). Bath application of DAMGO reduces IPSPs in the same neuron shown in top. In the presence of DAMGO, stimulation of local inhibition fails to block AP generation while depolarizing neurons (middle, right). E, DAMGO reduces IPSP amplitude in 4 of 6 neurons recorded. F, DAMGO reduces integrated IPSP area in 6 of 6 neurons. *p < 0.05. G, Under control conditions, inhibition blocks AP generation. *p < 0.05. H, In the presence of DAMGO, inhibition fails to significantly block AP generation; 1 of 6 neurons was still blocked by inhibition. A–C, Data are mean ± SEM.