Actions of cannabinoids on membrane properties and synaptic transmission in rat periaqueductal gray neurons in vitro

Christopher W. Vaughan*, Mark Connor, Elena E. Bagley, Macdonald J. Christie

*Corresponding author for this work

Research output: Contribution to journalArticle

201 Citations (Scopus)

Abstract

The midbrain periaqueductal gray (PAG) is a major site of cannabinoid- mediated analgesia in the central nervous system. In the present study, we examined the actions of cannabinoids on rat PAG neurons in vitro. In brain slices, superfusion of the cannabinoid receptor agonist WIN55,212-2 inhibited electrically evoked inhibitory and excitatory postsynaptic currents in all PAG neurons. The endogenous cannabinoid anandamide inhibited evoked inhibitory postsynaptic currents in the presence of the anandamide transport inhibitor AM404, but not in its absence. The stable anandamide analog R1- methanandamide also inhibited evoked inhibitory postsynaptic currents. WIN55,212-2 reduced the rate of spontaneous miniature inhibitory postsynaptic currents in normal and Ca2+-free solutions, but had no effect on their amplitude distributions or kinetics. The WIN55,212-2-induced decrease in miniature inhibitory postsynaptic current rate was concentration dependent (EC50 = 520 nM). The effects of cannabinoids were reversed by the CB1 receptor antagonist SR141716. WIN55,212-2 produced no change in membrane current or conductance in PAG neurons in brain slices and had no effect on Ca2+-channel currents in acutely isolated PAG neurons. These findings suggest that cannabinoids act via CB1 receptors to inhibit GABAergic and glutamatergic synaptic transmission in rat PAG, although the efficacy of endogenous cannabinoids is likely to be limited by uptake and breakdown. Like μ-opioids, cannabinoids act to reduce the probability of transmitter release from presynaptic terminals via a Ca2+-independent mechanism. In contrast to μ-opioids, cannabinoids have no direct postsynaptic actions on PAG neurons. Thus, cannabinoids and μ-opioids are likely to produce analgesia within PAG in part by different mechanisms.

Original languageEnglish
Pages (from-to)288-295
Number of pages8
JournalMolecular Pharmacology
Volume57
Issue number2
Publication statusPublished - 2000
Externally publishedYes

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