The effect of naloxone on opioid-induced inhibition and facilitation of acetylcholine release in brain slices.

1 The effect of morphine, methionine-enkephalin (Met-enkephalin) and D-Ala2-D-Leu5-enkephalin (DADLE) were tested on the spontaneous and electrically-evoked release of acetylcholine (ACh) from superfused slices of guinea-pig thalamus, caudate nucleus and cerebral cortex. 2 At no concentration did morphine, Met-enkephalin or DADLE modify the outflow of ACh at rest but Met-enkephalin in the presence of naloxone, reduced the resting ACh release. 3 Morphine, at a low dose (3 microM) had no effect in slices of cerebral cortex, but it enhanced the evoked release of ACh in thalamic and caudate, slices. At higher doses of morphine (10-30 microM), the ACh release evoked by electrical pulses was significantly inhibited in every area. 4 Met-enkephalin behaved like morphine in thalamic slices, whereas DADLE, a specific delta agonist, produced a slight inhibition of ACh outflow only at 10 microM. 5 Naloxone antagonized the inhibitory effect of morphine in the cerebral cortex and caudate nucleus slices. Naloxone and also spiroperidol blocked the releasing effect of morphine in caudate slices. In contrast naloxone did not affect the increase of ACh release caused by morphine and Met-enkephalin in thalamic slices. The inhibitory effect of both opioids at high doses was reversed by naloxone so that they then enhanced ACh release. 6 A two fold increase of calcium concentration in the Krebs solution prevented the inhibitory effects of morphine 10 microM. 7 It is suggested that two receptors are present in thalamic slices, one of which inhibits and the other facilitates ACh release.