Pharmacological modulation of GABAA receptor-mediated postsynaptic potentials in the CA1 region of the rat hippocampus |
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Authors: | Nicholas A Manuel Ceri H Davies |
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Affiliation: | 1.Department of Pharmacology, University of Edinburgh, 1 George Square, Edinburgh EH8 9JZ |
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Abstract: | - It is unclear whether GABAA receptor-mediated hyperpolarizing and depolarizing synaptic potentials (IPSPAs and DPSPAs, respectively) are evoked by (a) the same populations of GABAergic interneurones and (b) exhibit similar regulation by allosteric modulators of GABAA receptor function. We have attempted to address these questions by investigating the effects of (a) known agonists for presynaptic receptors on GABAergic terminals, and (b) a range of GABAA receptor ligands, on each response.
- The GABA uptake inhibitor NNC 05-711 (10 μM) enhanced whereas bicuculline (10 μM) inhibited both IPSPAs and DPSPAs.
- (−)-Baclofen (5 μM), [D-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin (DAGO; 0.5 μM), and carbachol (10 μM) caused substantial depressions (up to 99%) of DPSPAs that were reversed by CGP 55845A (1 μM), naloxone (10 μM) and atropine (5 μM), respectively. In contrast, 2-chloroadenosine (CADO; 10 μM) only slightly depressed DPSPAs. Quantitatively, the effect of each agonist was similar to that reported for IPSPAs.
- The neurosteroid ORG 21465 (1–10 μM), the anaesthetic propofol (50–500 μM), the barbiturate pentobarbitone (100–300 μM) and zinc (50 μM) all enhanced DPSPAs and IPSPAs.
- The benzodiazepine (BZ) agonist flunitrazepam (10–50 μM) and inverse agonist DMCM (1 μM) caused a respective enhancement and inhibition of both IPSPAs and DPSPAs. The BZω1 site agonist zolpidem (10–30 μM) produced similar effects to flunitrazepam.
- The anticonvulsant loreclezole (1–100 μM) did not affect either response.
- These data demonstrate that similar populations of inhibitory interneurones can generate both IPSPAs and DPSPAs by activating GABAA receptors that are subject to similar allosteric modulation.
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Keywords: | Baclofen carbachol DAGO benzodiazepine GABAA receptors ORG 21465 propofol zinc zoplidem |
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