Changes in hippocampal circuitry after pilocarpine-induced seizures as revealed by opioid receptor distribution and activation.
The pilocarpine model of temporal lobe epilepsy was used to study the time-dependent changes in dentate gyrus circuitry after seizures. Seizures caused a decrease in mu- and delta-opioid receptor immunoreactive (MOR-IR and DOR-IR, respectively) neurons in the hilus and MOR-IR neurons in the granule cell layer. Additionally, diffuse DOR-IR, MOR-IR, and GABA immunoreactivities (GABA-IR) were increased in the inner molecular layer. Using the in vitro hippocampal slice preparation to study the physiological consequences of the anatomical changes, we found that the disinhibitory effects of the mu-opioid receptor agonist [D-Ala2, MePhe4,Gly-(ol)5]-enkephalin (DAMGO) and the GABAA receptor antagonist bicuculline were greatly depressed 5-13 d after pilocarpine injection but returned to control levels within 6 weeks. The amplitudes of monosynaptic evoked IPSCs and the effects of DAMGO on this parameter were also slightly decreased 5-13 d after pilocarpine injection but significantly increased at 6 weeks. DAMGO significantly decreased the mean amplitude of spontaneous IPSCs (sIPSCs) at 6 weeks after pilocarpine injection but not in controls. The delta-opioid receptor agonist [D-Pen2,5]-enkephalin (DPDPE) principally inhibited excitatory transmission 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 results illustrate the anatomical reorganization and functional changes in dentate gyrus circuitry evident in an animal model of temporal lobe epilepsy and provide evidence of compensatory changes after trauma to the hippocampal formation.
Bausch
S B
SB
Department of Pharmacology, University of Washington, Seattle, Washington 98195-7280, USA.
Chavkin
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C
D000818:Animals; D018891:Dentate Gyrus / Q000378:metabolism / Q000503:physiopathology*; D004833:Epilepsy, Temporal Lobe / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D009434:Neural Pathways / Q000378:metabolism / Q000503:physiopathology; D010862:Pilocarpine; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000378:metabolism*; D017465:Receptors, Opioid, delta / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000378:metabolism; D014018:Tissue Distribution; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D010862:Pilocarpine; D005680:gamma-Aminobutyric Acid