Article date: May 2003
By: Christopher W Vaughan, Elena E Bagley, Geoffrey M Drew, Alwin Schuller, John E Pintar, Stephen P Hack, MacDonald J Christie in Volume 139, Issue 2, pages 362-367
Patch clamp recordings were made from periaqueductal grey (PAG) neurons in vitro to investigate the cellular actions of opioids in wild‐type C57B16/J mice and mutant mice lacking the first exon of the μ‐opioid (MOP) receptor.
In wild‐type mice, the κ‐(KOP) agonist U‐69593 (300 nM) and the mixed μ/δ‐opioid agonist met‐enkephalin (10 μM), but not the δ‐(DOP) agonist deltorphin (300 nM), reduced the amplitude of evoked GABAA‐mediated inhibitory postsynaptic currents (IPSCs). Met‐enkephalin and U‐69593 also reduced the rate of spontaneous miniature IPSCs, but had no effect on their amplitude and kinetics. In μ‐receptor‐deleted mice, only U‐69593 (300 nM) reduced the amplitude of evoked IPSCs.
In wild‐type mice, the MOP agonist DAMGO (3 μM) produced an outward current in 76% of the neurons. Deltorphin and U‐69593 produced outward currents in 24 and 32% of the neurons, respectively. In μ‐receptor‐deleted mice, deltorphin and U‐69593 produced similar outward currents in 32 and 27% of the neurons, respectively, while DAMGO was without effect. All neurons in both the wild‐type and μ‐receptor‐deleted mice responded with similar outward currents to either the GABAB receptor agonist baclofen (10 μM), or the opioid‐like receptor ORL1 (NOP) agonist nociceptin (300 nM).
The DAMGO‐, deltorphin‐, U‐69593‐, baclofen‐ and nociceptin‐induced currents displayed inward rectification and reversed polarity at −109 to −116 mV.
These findings indicate that μ‐, δ‐ and κ‐opioid receptor activation has complex pre‐ and postsynaptic actions within the mouse PAG. This differs to the rat PAG where only μ‐opioid receptor actions have been observed.
Patch clamp recordings were made from periaqueductal grey (PAG) neurons in vitro to investigate the cellular actions of opioids in wild‐type C57B16/J mice and mutant mice lacking the first exon of the μ‐opioid (MOP) receptor.
In wild‐type mice, the κ‐(KOP) agonist U‐69593 (300 nM) and the mixed μ/δ‐opioid agonist met‐enkephalin (10 μM), but not the δ‐(DOP) agonist deltorphin (300 nM), reduced the amplitude of evoked GABAA‐mediated inhibitory postsynaptic currents (IPSCs). Met‐enkephalin and U‐69593 also reduced the rate of spontaneous miniature IPSCs, but had no effect on their amplitude and kinetics. In μ‐receptor‐deleted mice, only U‐69593 (300 nM) reduced the amplitude of evoked IPSCs.
In wild‐type mice, the MOP agonist DAMGO (3 μM) produced an outward current in 76% of the neurons. Deltorphin and U‐69593 produced outward currents in 24 and 32% of the neurons, respectively. In μ‐receptor‐deleted mice, deltorphin and U‐69593 produced similar outward currents in 32 and 27% of the neurons, respectively, while DAMGO was without effect. All neurons in both the wild‐type and μ‐receptor‐deleted mice responded with similar outward currents to either the GABAB receptor agonist baclofen (10 μM), or the opioid‐like receptor ORL1 (NOP) agonist nociceptin (300 nM).
The DAMGO‐, deltorphin‐, U‐69593‐, baclofen‐ and nociceptin‐induced currents displayed inward rectification and reversed polarity at −109 to −116 mV.
These findings indicate that μ‐, δ‐ and κ‐opioid receptor activation has complex pre‐ and postsynaptic actions within the mouse PAG. This differs to the rat PAG where only μ‐opioid receptor actions have been observed.
British Journal of Pharmacology (2003) 139, 362–367. doi:10.1038/sj.bjp.0705261
DOI: 10.1038/sj.bjp.0705261
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