Molecular neuroscienceEffects of gamma hydroxybutyric acid on inhibition and excitation in rat neocortex
Section snippets
Slice preparation
Frontal cortical slices were prepared from male, Sprague–Dawley rats (PD20–30, Charles River Laboratories, Raleigh, NC, USA). Animals were handled and housed according to the guidelines of the National Institutes of Health Committee on Laboratory Animal Resources. All experimental procedures or protocols were approved by Animal Care and Use Committee of Duke University and Durham VA Medical Center. The minimum number of animals needed to obtain statistically significant results was used. All
GHB effects on mono-synaptic IPSCs
Evoked mono-synaptic IPSCs were recorded from cortical pyramidal cells held at 0 mV in the presence of the excitatory amino acid antagonists APV (50 μM) and DNQX (20 μM). Bicuculline sensitive outward currents were continuously observed and the GHB effect was assessed. As shown in Fig. 1A, bath application of GHB (1 mM) for 20 min decreased the peak amplitude of IPSCs by 22% of control. The GHB effects were reversed after addition of the GABAB receptor antagonist CGP 62349 (5 μM). The GHB
Discussion
In the rat neocortical slice we found that GHB reduced monosynaptic evoked GABAA IPSCs in agreement with previously demonstrated reductions of spontaneous action potential–dependent IPSCs (Jensen and Mody, 2001) and reductions of GABA release as measured using microdialysis (Hu et al., 2000). The greater reduction of polysynaptic IPSCs is also expected if GHB is reducing synaptic excitation of interneurons and perhaps hyperpolarizing interneurons (Jensen and Mody, 2001). Thus GHB appears to act
Acknowledgments
The authors wish to acknowledge the generous support of the National Institute of Drug Abuse (DA 014931).
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