Fig. 1. Experimental design depicted on a timeline.

All Tat transgenic mice received DOX-containing chow for 8 weeks and were repeatedly injected with morphine (10 – 40 mg/kg, increasing by 10 mg/kg/2 day, s.c., b.i.d.) or saline for the last 2 weeks. Mice in cohort 1 were single housed starting at week 5 of DOX administration to establish territorial behavior. Then on day 14 of repeated morphine injections cohort 1 mice were tested in assays of aggressive sociability, the social dominance tube and resident-intruder tests. On day 14 of repeated morphine injections mice in cohort 2 were tested in the novel environment non-reciprocal social interaction and social novelty assays. The day following behavioral testing, mice in both cohorts were euthanized and tissues were randomly assigned to immunoblotting and ELISA or immunohistochemistry assays.