D-1 AGONISTS SUPPRESS ZERO MG2+-INDUCED EPILEPTIFORM ACTIVITY IN THE RAT CINGULATE CORTEX SLICE

THIS study determined whether dopamine can influence epileptiform activity in vitro through an action at D-1 receptors. Dopamine (50-1000 mu M) and the selective D-1 agonists SKF 38393, SKF 75670, SKF 80723 and SKF 82526 (10-250 mu M) suppressed the paroxysmal discharges produced in rat cingulate cortex slices by the omission of Mg2+ from the bathing medium. These antiepileptic effects were mimicked by forskolin (10-100 mu M), blocked by the D-1 antagonist SCH 39166 (0.5 mu M), facilitated by IBMX (500 mu M) and unaffected by propranolol (2 mu M), suggesting the participation of cyclic AMP in the D-1 response. Possible mechanisms, including direct postsynaptic inhibition, modulatory enhancement of GABA activity and presynaptic inhibition of glutamate release are considered.