Local administration of morphine decreases the extracellular level of GABA in the periaqueductal gray matter of freely moving rats

Opioids are generally believed to activate descending pain inhibitory pathways from the periaqueductal gray matter (FAG). Since opioids exert an inhibitory effect on neural excitability and transmitter release, an opioid-mediated inhibition of tonically active inhibitory gamma-aminobutyric acid (GABA) neurons has been suggested to mediate this effect. The aim of the present microdialysis study was to investigate the effect of local administration of morphine on the extracellular GABA level in the FAG of awake rats. The recently developed and highly sensitive method of capillary electrophoresis with laser-induced fluorescence detection was used for GABA determination in microdialysate samples obtained from the FAG of freely moving rats. The basal GABA level was 54.5 +/- 6.6 nM (n = 8; mean +/- SEM). Perfusion of the dialysis probe with morphine (100 mu M) for 30 min significantly decreased the GABA level to 28.2 +/- 4.2 nM (n = 8; P < 0.05). The effect of morphine was reversed by coperfusion with naloxone (100 mu M in the perfusion fluid). The present results thus provide direct experimental evidence for an opioid-induced inhibition of tonic GABA release in the FAG, which may in turn lead to a disinhibition of descending pain inhibitory pathways.