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 population of intrinsic interneurons of the striatum. Production of nitric oxide in the nNOS-containing neurons is sensitive to dopamine stimulation. Using quantitative in situ hybridization, the present study investigated the alteration in basal nNOS mRNA expression in striatal nNOS-containing neurons of mice treated with the psychostimulant amphetamine or a full D1 dopamine receptor agonist, SKF-82958. A single systemic injection of amphetamine induced a dose-related change in striatal nNOS mRNA expression. Whereas amphetamine at 4 mg/kg decreased basal levels of nNOS mRNA in both the dorsal (caudoputamen) and ventral (nucleus accumbens) striatum, the drug at a higher dose (12 mg/kg) increased nNOS expression in the two regions. Similarly, an acute 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 data indicate that constitutive nNOS expression in nitric oxide-producing neurons of the mouse striatum is regulated by dopaminergic transmission. Altered nNOS expression may result in changes in nitric oxide synthesis and thus contribute to biological actions of dopamine stimulants.