Fig. 1.

Experimental design depicted on a timeline. All Tat transgenic mice received DOX-containing chow for 3 months and were then subcutaneously (s.c.) injected with saline or morphine for 8 days, except for a separate set of mice that were PET imaged as control animals (no injections), which received DOX for 2 weeks. Body mass was recorded daily. On day 9 after morphine administration, mice were tested for baseline activity in the tail-flick and hot-plate assays. This was followed by four acute, cumulative s.c. morphine injections with a 20-min wait period after each injection before tail-flick responses to warm-water and hindpaw lick or lift to a heated hot-plate were tested. At the end of behavioral testing, animals were sacrificed immediately and brains were taken for immunohistochemistry and mass spectrometry analysis. Cytokine analyses were conducted on a separate set of animals. TF tail-flick assay, HP hot-plate assay, PET positron emission tomography, MS mass spectrometry, Cytokine cytokine analyses; n = mice per group