CHANGES IN HIPPOCAMPAL CIRCUITRY AFTER PILOCARPINE-INDUCED SEIZURES AS REVEALED BY OPIOID RECEPTOR DISTRIBUTION AND ACTIVATION

The pilocarpine model of temporal robe epilepsy was used to study the time-dependent changes in dentate gyrus circuitry after seizures. Seiz ures caused a decrease in mu- and delta-opioid receptor immunoreactive (MOR-IR and DOR-IR, respectively) neurons in the hilus and MOR-IR neu rons in the granule cell layer. Additionally, diffuse DOR-IR, MOR-IR, and GABA immunoreactivities (GABA-IR) were increased in the inner mole cular layer. Using the in vitro hippocampal slice preparation to study the physiological consequences of the anatomical changes, we found th at the disinhibitory effects of the mu-opioid receptor agonist [D-Ala( 2),MePhe(4),Gly-(ol)(5)]-enkephalin (DAMGO) and the GABA(A) receptor a ntagonist bicuculline were greatly depressed 5-13 d after pilocarpine injection but returned to control levels within 6 weeks. The amplitude s of monosynaptic evoked IPSCs and the effects of DAMGO on this parame ter were also slightly decreased 5-13 d after pilocarpine injection bu t significantly increased at 6 weeks. DAMGO significantly decreased th e mean amplitude of spontaneous IPSCs (sIPSCs) at 6 weeks after piloca rpine injection but not in controls. The delta-opioid receptor agonist [D-Pen(2,5)]-enkephalin (DPDPE) principally inhibited excitatory tran smission in saline-treated animals without affecting either sIPSCs or evoked IPSCs. The DPDPE-induced inhibition of excitatory transmission became more pronounced at 6 weeks after pilocarpine injection. These r esults illustrate the anatomical reorganization and functional changes in dentate gyrus circuitry evident in an animal model of temporal lob e epilepsy and provide evidence of compensatory changes after trauma t o the hippocampal formation.