Research paperEffects of dopamine D1 receptor activation and blockade on dopamine and noradrenaline levels in the rat brain

•A functional relationship between the dopaminergic and noradrenergic systems.•We examine the role of D1 receptors on noradrenergic and dopaminergic responses.•The activation of D1 receptors modulates the response of the noradrenergic system.•The blockade of D1 receptors attenuates the effects induced by the activation.

The noradrenergic and dopaminergic systems are associated with the motor system and have anatomical and functional connections that have not yet been studied. The present study aimed to examine the specific role of D1 receptors (D1Rs) on noradrenergic and dopaminergic responses in the rat brain. Male Wistar rats were assigned to eight groups to receive systemic injection of a D1R agonist (SKF-38393) at 0, 1, 5 or 10 mg/kg or injection of a D1R antagonist (SCH-23390) at 0, 0.25, 0.5 or 1 mg/kg. Dopamine (DA) and noradrenaline (NA) levels were measured using high-performance liquid chromatography. Injection of SKF-38393 alone at 1, 5 and 10 mg/kg did not alter DA levels in the midbrain, cerebral cortex or pons, while it significantly increased these levels in the striatum (at 1 and 10 mg/kg), hippocampus (at 1 mg/kg) and cerebellum (at 1 and 5 mg/kg). Administration of SKF-38393 at 1, 5, and 10 mg/kg decreased the NA levels in the midbrain, pons, hippocampus (except at 1 mg/kg) and cortex (except at 5 mg/kg), whereas the opposite effect was observed in the striatum. SCH-23390 decreased the DA levels in the cortex (at 0.25 and 0.5 mg/kg) and pons (at 0.5 mg/kg). In contrast, 0.25, 0.5 and 1 mg/kg SCH-23390 increased the DA levels in the cerebellum, whereas no differences from the control levels were observed for the DA levels in the striatum, midbrain and hippocampus. SCH-23390 at 0.5 and 1 mg/kg increased the NA levels in the striatum. In contrast, the midbrain, hippocampus, cortex, pons and cerebellum did not exhibit altered NA levels. Our results demonstrate that the activation of D1Rs modulates the response of the noradrenergic system in nearly all of the investigated brain structures; thus, the blockade of D1Rs attenuates the effects induced by D1R activation.