Chronic benzodiazepine treatment of rats induces reduction of paired-pulse inhibition in CA1 region of in vitro hippocampus.
Paired-pulse inhibition was studied extracellularly in in vitro hippocampal slices from rats sacrificed 48 h or 7 days after 1 week flurazepam (FZP) treatment. Population spikes and field excitatory postsynaptic potentials (EPSPs) were recorded with NaCl-containing glass micropipettes in the stratum pyramidale and stratum radiatum, respectively, of the CA1 region. Conditioning pulses were delivered by stimulating Shaffer collaterals (orthodromic) or the alveus (antidromic). Orthodromic test pulses were delivered with interpulse intervals of 10-200 ms. There was a significant reduction in paired-pulse inhibition in slices from treated vs control rats in both the orthodromic-orthodromic and antidromic-orthodromic paradigms. Reduced inhibition was evident 48 h, but not 7 days, after the end of FZP treatment. Furthermore, there was a significant prolongation of the half decay time of the field EPSP, without a significant change in the initial slope or maximum amplitude. The results may suggest an impairment of endogenous gamma-aminobutyric acid function in the hippocampus after chronic benzodiazepine (BZ) treatment and may provide a basis for a mechanism of BZ tolerance.
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Department of Pharmacology, Medical College of Ohio, Toledo 43699.
Tietz
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D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D004558:Electric Stimulation; D005071:Evoked Potentials / Q000187:drug effects; D005479:Flurazepam / Q000008:administration & dosage*; D006624:Hippocampus / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D005479:Flurazepam