PROGESTERONE IN-VITRO INCREASES NMDA-EVOKED [H-3] DOPAMINE RELEASE FROM STRIATAL SLICES IN PROESTRUS RATS

The dopaminergic nerve terminals in rat striatum appear to be an impor tant target for progesterone (Pg) and the excitatory amino acid glutam ate. In the present study the possible interaction between glutamate a nd Pg upon [H-3]DA release in striatal slices from rats in proestrus w as examined. [H-3]DA release was augmented by NMDA in a concentration- dependent manner. The presence of Pg (400 nM) in the perfusion medium produced an amplification of the responses to NMDA (50 mu M) as shown by significant increase in the tritium outflow. The NMDA selective ant agonists AP-7 (100 mu M) and MK-801 (0.1 mu M) prevented the effects o f both NMDA and NMDA plus Pg on [H-3]DA release. In contrast, the AMPA /kainate receptor antagonist CNQX (10 and 20 mu M) was ineffective. Fu rthermore, AP-7 (100 mu M) attenuated the enhancing effect of 400 nM P g on [H-3]DA release evoked by 28 mM K+. The antagonist was unable to alter the effect produced by K+ alone. These results indicate a specif ic action of Pg on dopaminergic terminals mediated by NMDA receptors a nd suggest a close interaction between glutamate and dopamine systems in the striatum, apparently modulated by progesterone.