Cellular actions of opioids on periaqueductal grey neurons from C57B16/J mice and mutant mice lacking MOR-1

摘要

class="enumerated" style="list-style-type:decimal">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.