Psychopharmacology

, Volume 198, Issue 4, pp 539–549 | Cite as

Distinctions among GABAA and GABAB responses revealed by calcium channel antagonists, cannabinoids, opioids, and synaptic plasticity in rat hippocampus

Original Investigation

Abstract

Rationale

Hippocampal interneurons release γ-aminobutyric acid (GABA) and produce fast GABAA- and slow GABAB-inhibitory postsynaptic potentials (IPSPs). The regulation of GABAB eIPSPs or the interneurons that produce them are not well understood. In addition, while both μ-opioid receptors (μORs) and cannabinoid CB1R receptors (CB1Rs) are present on hippocampal interneurons, it is not clear how these two systems interact.

Objectives

This study tests the hypotheses that: (1) all interneurons can initiate both GABAA and GABAB inhibitory postsynaptic potentials; (2) GABAB responses are insensitive to mGluR-triggered, endocannabinoid (eCB)-mediated inhibitory long-term depression (iLTD); (3) GABAB responses are produced by interneurons that express μOR; and (4) CB1R-dependent and μOR-dependent response interact.

Materials and methods

Pharmacological and electrophysiological approaches were used in acute rat hippocampal slices. High resistance microelectrode recordings were made from pyramidal cells, while interneurons were stimulated extracellularly.

Results

GABAB responses were found to be produced by interneurons that release GABA via either presynaptic N-type or P/Q-type calcium channels but that they are insensitive to suppression by eCBs or eCB-mediated iLTD. GABAB IPSPs were sensitive to suppression by a μOR agonist, suggesting a major source of GABAB responses is the μOR-expressing interneuron population. A small eCB-iLTD (10% eIPSP reduction) persisted in conotoxin. eCB-iLTD was blocked by a μOR agonist in 6/13 slices.

Conclusions

GABAB responses cannot be produced by all interneurons. CB1R or μOR agonists will differentially alter the balance of activity in hippocampal circuits. CB1R- and μOR-mediated responses can interact.

Keywords

DAMGO mGluR Endocannabinoid CB1R CA1 iLTD SR141716A Agatoxin Conotoxin Paired-pulse ratio 

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Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  1. 1.Departments of Physiology and PsychiatryUniversity of Maryland School of MedicineBaltimoreUSA
  2. 2.Program in NeuroscienceUniversity of Maryland School of MedicineBaltimoreUSA

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