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

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 n M ) and the mixed μ / δ ‐opioid agonist met‐enkephalin (10 μ M ), but not the δ ‐(DOP) agonist deltorphin (300 n M ), reduced the amplitude of evoked GABA A ‐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 n M ) reduced the amplitude of evoked IPSCs. In wild‐type mice, the MOP agonist DAMGO (3 μ M ) 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 GABA B receptor agonist baclofen (10 μ M ), or the opioid‐like receptor ORL1 (NOP) agonist nociceptin (300 n M ). 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