Inhibition by agmatine on morphine-induced conditioned place preference in rats

Our previous studies demonstrated the ability of exogenous agmatine to inhibit tolerance to and physical dependence on morphine in mice, rats and monkeys. The present study further evaluated the effect of agmatine on the psychological dependence induced by morphine in conditioned place preference assay. Agmatine (0.75-20 mg/kg, s.c.) co-administered with morphine during the conditioning sessions completely abolished the acquisition of morphine-induced conditioned place preference in rats, which was associated with activation of imidazoline receptors. Agmatine (0.75-10 mg/kg, s.c.) administered on the test day inhibited the expression of the place preference. After 30 days of extinction of conditioned place preference, agmatine 2.5 and 40 mg/kg inhibited the priming effect of morphine 0.5 mg/kg on the place preference. Furthermore, agmatine inhibited the increased expression of FosB in the nucleus accumbens caused by chronic morphine. All these results suggest that agmatine could inhibit morphine-induced psychological dependence and relapses by affecting the expression of transcription factor FosB.