Co. Stiller et al., LOCAL-ADMINISTRATION OF MORPHINE DECREASES THE EXTRACELLULAR LEVEL OFGABA IN THE PERIAQUEDUCTAL GRAY-MATTER OF FREELY MOVING RATS, Neuroscience letters, 209(3), 1996, pp. 165-168
Opioids are generally believed to activate descending pain inhibitory
pathways from the periaqueductal gray matter (FAG). Since opioids exer
t an inhibitory effect on neural excitability and transmitter release,
an opioid-mediated inhibition of tonically active inhibitory gamma-am
inobutyric acid (GABA) neurons has been suggested to mediate this effe
ct. The aim of the present microdialysis study was to investigate the
effect of local administration of morphine on the extracellular GABA l
evel in the FAG of awake rats. The recently developed and highly sensi
tive method of capillary electrophoresis with laser-induced fluorescen
ce 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 prob
e 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 wa
s reversed by coperfusion with naloxone (100 mu M in the perfusion flu
id). 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 path
ways.