Enhancement of opioid inhibition of GABAergic synaptic transmission by cyclo‐oxygenase inhibitors in rat periaqueductal grey neurones

• Published in: British journal of pharmacology Vol. 123; no. 8; pp. 1479 - 1481
• Main Author: Vaughan, C. W.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.04.1998; Nature Publishing
• Subjects: analgesia; Analgesics; Analgesics, Opioid - pharmacology; Animals; Biological and medical sciences; central nervous system; Cyclooxygenase 1; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors - pharmacology; cyclo‐oxygenase; GABA; gamma-Aminobutyric Acid - physiology; In Vitro Techniques; Isoenzymes - metabolism; Medical sciences; Membrane Proteins; Morphine - pharmacology; Narcotics - pharmacology; Neurons - drug effects; Neuropharmacology; Opioid; Periaqueductal Gray - cytology; Periaqueductal Gray - drug effects; periaqueductal grey; Pharmacology. Drug treatments; Prostaglandin-Endoperoxide Synthases - metabolism; Rats; Rats, Sprague-Dawley; Special Report; synaptic transmission; Synaptic Transmission - drug effects; Prostaglandin-endoperoxide synthase; Rat; Enzyme; Isozyme; Rodentia; Central nervous system; Gabaergic transmission; Enzyme inhibitor; Morphine; Opiates; Narcotic analgesic; In vitro; Non steroidal antiinflammatory agent; Vertebrata; Mammalia; Neuron; Periaqueductal gray matter; Animal; Oxidoreductases
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1038/sj.bjp.0701818

Cyclo‐oxygenase (COX) inhibitors potentiate opioid inhibition of GABAergic synaptic transmission in rat periaqueductal grey (PAG) (Vaughan et al., 1997). In the present study, the relative contribution of cyclo‐oxygenase‐1 (COX‐1) and COX‐2 inhibition to this phenomenon was examined by use of whole‐cell patch clamp recordings in brain slices. The μ‐receptor partial agonist morphine (10 μM) had little effect on GABAergic synaptic transmission. Morphine reduced the frequency of spontaneous miniature inhibitory postsynaptic currents (m.i.p.s.cs) by 13%. The nonselective COX inhibitor, indomethacin, produced a dose‐dependent potentiation of the morpine inhibition of m.i.p.s.c. frequency (maximum inhibition 42%, IC50=6 nM). More selective COX‐2 inhibitors produced a similar potentiation of the morphine inhibition of m.i.p.s.c. frequency; however, at greater concentrations (IC50=57 nM piroxicam, 1.7 μM DFU). Maintaining slices in the protein synthesis inhibitor cycloheximide (1 μM), to prevent COX‐2 induction, had no effect on the potentiation action of DFU (10 μM). These results demonstrate that the potentiation of opioid inhibition of GABAergic synaptic transmission in PAG is largely a result of inhibition of COX‐1 activity. These findings suggest that COX‐1, rather than COX‐2 inhibition, mediates the synergistic analgesic actions of opioids and non‐steroidal anti‐inflammatory drugs (NSAIDs) in the midbrain PAG. British Journal of Pharmacology (1998) 123, 1479–1481; doi:10.1038/sj.bjp.0701818