Agmatine inhibits morphine-induced drug discrimination in rats

Our previous studies have shown that agmatine inhibited morphine-induced conditioned place preference and locomotor sensitization in rats. In the present study, we further investigated the effects of agmatine on the discriminative stimulating effects produced by morphine in rats. Agmatine, at the dose range of 10–80 mg/kg (i.g.), neither induced drug discrimination, nor substituted for morphine stimulus in rats that were previously treated with morphine, suggesting that agmatine itself has no psychomotor-stimulating potential. However, pretreatment with agmatine (40, 80 mg/kg, i.g.) significantly inhibited the acquisition, but not expression, of morphine-induced drug discrimination as assessed by the correct nose-poke response. Further, chronic administration of agmatine (40, 80 mg/kg/day × 12 days, i.g., 25 min prior to morphine) also significantly accelerated the extinction of the discrimination induced by morphine. These data suggest that agmatine inhibits the acquisition and accelerates the extinction of morphine-induced discrimination, supporting possible use of agmatine in the treatment of opioid dependence.