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Volume 17, Number 1,
Issue of January 1, 1997
pp. 477-492
Copyright ©1997 Society for Neuroscience
Changes in Hippocampal Circuitry after Pilocarpine-Induced
Seizures as Revealed by Opioid Receptor Distribution and
Activation
Received Feb. 13, 1996; revised Sept. 24, 1996; accepted Oct. 17, 1996.
Suzanne B. Bausch and
Charles Chavkin
Department of Pharmacology, University of Washington, Seattle,
Washington 98195-7280
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 µ- and -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 µ-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 -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.
Key words:
dentate gyrus;
epilepsy;
GABA;
hippocampus;
mossy fiber
sprouting;
neurotoxicity;
synaptic inhibition;
opiate physiology
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