FIGURE 1.
Experimental Design: For 6 consecutive days, mice received intraperitoneal injections of 5 mg/kg morphine (* another group of mice received saline injections instead) twice-daily. On day 7, 2 hr after their AM morphine (or saline) injection, mice received an intraperitoneal injection of one of the five treatments: ** free naloxone (8 mg/kg), Nal-cNP (Hi)—8 mg/kg naloxone, Nal-cNP (Low)—0.7 mg/kg naloxone, cNP-empty, or saline. Behavior was video recorded for 6 hr (beginning immediately after the treatment injection). On days 8 and 9 video recording began 24 hr (day 8) and 48 hr (day 9) after the treatment injection was given (day 7) and behavior was recorded for 15 min. Precipitated opioid withdrawal behavior (naloxone-induced jumping, rearing, forepaw tremors, wet dog shakes, and forepaw licking) was measured the first 15 min of each hr. Figure prepared with BioRender.com software