Cannabinoid receptor activation inhibits GABAergic neurotransmission in rostral ventromedial medulla neurons in vitro
1999; Wiley; Volume: 127; Issue: 4 Linguagem: Inglês
10.1038/sj.bjp.0702636
ISSN1476-5381
AutoresChristopher W. Vaughan, Iain S. McGregor, MacDonald J. Christie,
Tópico(s)Sleep and Wakefulness Research
ResumoThe rostral ventromedial medulla (RVM) is thought to play a crucial role in the antinociceptive actions of cannabinoids. This study examined the actions of the cannabinoid receptor agonist, WIN55,212‐2, on membrane properties and GABAergic synaptic transmission in RVM neurons using whole cell patch clamp recordings in brain slices. WIN55,212‐2 (3 μ M ) had no effect on membrane K + conductance of primary or secondary RVM neurons. Primary neurons responded to the κ‐opioid receptor agonist U69,593 (300 n M –1 μ M ). Secondary neurons responded to the μ,δ‐opioid receptor agonist met‐enkephalin (10 μ M ). WIN55,212‐2 reduced the amplitude of electrically evoked (GABAergic) inhibitory postsynaptic currents (IPSCs) in all neurons (58%, pEC 50 =6.2±0.1). The inhibition was reversed by the CB 1 receptor selective antagonist, SR141716 (3 μ M ). WIN55,212‐2 also produced relative facilitation of the second IPSC to paired evoked IPSCs. WIN55,212‐2 and met‐enkephalin reduced the rate of spontaneous miniature IPSCs in all cells (44 and 53%), but had no effect on their amplitude distributions or kinetics. These results suggest that the antinociceptive actions of cannabinoids within RVM are primarily due to presynaptic inhibition of GABAergic neurotransmission. The neuronal substrates of cannabinoid actions in RVM therefore differ from those of opioids, which have both pre‐ and postsynaptic inhibitory actions. British Journal of Pharmacology (1999) 127 , 935–940; doi: 10.1038/sj.bjp.0702636
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