Abstract
Increased responsiveness to psychomotor stimulants can be produced by either chronic stimulant administration or by chronic dopamine receptor blockade. This study examined the role of nitric oxide in the development of neuroleptic-induced supersensitivity. N omega-nitro-L-arginine methyl ester hydrochloride (L-NAME) administered during chronic intraperitoneal (i.p.) haloperidol treatment (0.2 mg/kg/d for 14 d) was used to inhibit nitric oxide synthesis. Locomotor activity following a cocaine(i.p.) challenge injection (10 mg/kg) administered at 3 and 10 d after cessation of haloperidol treatment demonstrated the development of supersensitivity. Haloperidol animals pretreated with L-NAME i.p. (30 mg/kg) showed significantly less cocaine-stimulated locomotor activity on both tests than saline-pretreated animals. This finding suggests that nitric oxide is involved in haloperidol-induced supersensitivity and that a common neural mechanism may underlie the development of supersensitivity and stimulant-induced sensitization. This study also suggests that treatment with a nitric oxide synthesis inhibitor may decrease the side effects accompanying long-term treatment with antipsychotic medications.
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