Dose-related alteration in nitric oxide synthase mRNA expression induced by amphetamine and the full D1 dopamine receptor agonist SKF-82958 in mouse striatum

Neuronal nitric oxide synthase (nNOS) is normally expressed in one populati on of intrinsic interneurons of the striatum. Production of nitric oxide in the nNOS-containing neurons is sensitive to dopamine stimulation. Using qu antitative in situ hybridization, the present study investigated the altera tion in basal nNOS mRNA expression in striatal nNOS-containing neurons of m ice treated with the psychostimulant amphetamine or a full D1 dopamine rece ptor agonist, SKF-82958. A single systemic injection of amphetamine induced a dose-related change in striatal nNOS mRNA expression. Whereas amphetamin e at 4 mg/kg decreased basal levels of nNOS mRNA in both the dorsal (caudop utamen) and ventral (nucleus accumbens) striatum, the drug at a higher dose (12 mg/kg) increased nNOS expression in the two regions. Similarly, an acu te systemic injection of SKF-82958 decreased and increased nNOS mRNA levels in the dorsal and ventral striatum at 2 and 4 mg/kg, respectively. These d ata indicate that constitutive nNOS expression in nitric oxide-producing ne urons of the mouse striatum is regulated by dopaminergic transmission. Alte red nNOS expression may result in changes in nitric oxide synthesis and thu s contribute to biological actions of dopamine stimulants. (C) 2001 Elsevie r Science Ireland Ltd. All rights reserved.