Role of nitric oxide in the acquisition and expression of apomorphine- or morphine-induced locomotor sensitization

In the present study, the effects of l-arginine, a nitric oxide (NO) precursor, and N G-nitro- l-arginine methyl ester ( l-NAME), a nitric oxide synthase (NOS) inhibitor, on apomorphine- or morphine-induced locomotor sensitization in male albino mice were investigated. Our data showed that subcutaneous (s.c.) injection of apomorphine (2–10 mg/kg) or morphine sulphate (5–50 mg/kg) significantly increased locomotor behaviour in a dose-dependent manner. Intraperitoneal (i.p.) administration of l-arginine (100 mg/kg) increased locomotor activity, whereas l-NAME (20 mg/kg) decreased it. l-Arginine and l-NAME increased and decreased apomorphine- or morphine-induced locomotions, respectively. The locomotor behavioural response was enhanced in mice pretreated with apomorphine (2 mg/kg, daily ×3 days) or morphine (10 mg/kg, daily ×3 days) alone, indicating that sensitization had developed. Administration of l-arginine 30 min before each of three daily doses of apomorphine or morphine increased the development of sensitization, while administration of l-NAME 30 min before each of three daily doses of apomorphine or morphine decreased the acquisition of sensitization induced by apomorphine or morphine. Administration of l-arginine significantly increased and l-NAME significantly and dose-dependently decreased the expression of both apomorphine- and morphine-induced sensitization. The results indicate that NO may be involved in the acquisition and expression of apomorphine- or morphine-induced sensitization.