In vivo NMDA/dopamine interaction resulting in Fos production in the limbic system and basal ganglia of the mouse brain

Glutamatergic and dopaminergic effects on molecular processes have been extensively investigated in the basal ganglia. It has been demonstrated that NMDA and dopamine D₁ and D₂ receptors interact in the regulation of signal transduction and induction of transcription factors. In the present experiments, NMDA/dopamine interactions were investigated in the normosensitive caudate nucleus, hippocampus and amygdala by monitoring Fos production. We demonstrated that NMDA and the D₁ receptor agonist SKF 38393 triggered Fos levels in a distinct, non-overlapping and region-specific pattern. NMDA injected intraperitoneally (i.p.) elevated Fos levels in all hippocampal subfields and the central amygdala, whereas SKF 38393 triggered Fos production in basomedial, cortical, medial amygdala and caudate nucleus. The NMDA receptor antagonist CGS 19755 prevented NMDA- and SKF 38393- triggered Fos production in all investigated brain areas. Similarly, the D₁ receptor antagonist SCH 23390 inhibited the effects produced by SKF 38393 or NMDA. The D₂ receptor antagonist sulpiride exerted synergistic and antagonistic effects on NMDA- and SKF 38393-triggered Fos production, in a region specific manner. These data suggest that NMDA and dopamine receptors regulate Fos production within the limbic system and basal ganglia through regionally differentiated but interdependent actions. (C) 2000 Elsevier Science B.V.