Fig. 1.

Experimental timeline. For 2 weeks, Tat⁺ and Tat⁻ transgenic mice in cohort 1 were administered doxycycline (DOX) supplemented chow to induce Tat expression. Starting on day 1 of DOX administration, cohort 1 mice were repeatedly injected with escalating doses of morphine (10 – 40 mg/kg, s.c., that was increased by 10 mg/kg increments at 2 day intervals) or saline (b.i.d.) for 2 weeks and the brains were harvested for immunohistochemistry. Cohort 2 mice received DOX for 4 weeks. During the final 2 weeks of DOX administration, starting on day 14, mice were additionally injected with the same escalating morphine dosing paradigm as in cohort 1. Mice were humanely euthanized, and the PFC, striatum, and hippocampus were dissected for immunoblotting.