Morinda citrifolia Linn. fruit extract mitigates heroin seeking behavior in mice

Abstract

Methanolic extract of Morinda citrifolia unripe fruit (MMC) was tested against heroin addiction using a mouse modified runway model of drug‑seeking. Habituation sessions were carried out for 10 min/d for 3 days. On day 0, the total run time of each mouse was noted (the start box to goal box) during the preconditioning test. This was followed by the conditioning session (30 min), in which the animals were conditioned with escalating doses of heroin hydrochloride (5, 10, 20, 40 and 40 mg/kg) for 5 days upon entry into the goal box. On day 6, the run time of each mouse, from start to goal box, was recorded during the post conditioning test. Extinction trials were performed for the next 5 days, in which no drug/saline was injected upon goal box entry. On day 13, a priming dose of heroin (8 mg/kg) was given to reinstate drug seeking in the mice. MMC given as oral doses (1, 3 and 5 g/kg) dose‑dependently prolonged the run time to reach the goal box, indicating MMC attenuated heroin reinforcement. Moreover, MMC (5 g/kg) was found to reverse the heroin‑seeking on extinction trial 1 and 2. MMC was also found to reverse heroin‑induced reinstatement in mice. This study demonstrates that MMC attenuated heroin seeking at different phases of drug self‑administration in a mouse modified runway model.