Changes in cortical ACh and GABA outflow during morphine withdrawal involve alpha-1 and alpha-2 receptors

Naloxone (0.3-9 μmol kg-1), electrical stimulation of locus ceruleus or clonidine at low doses (7.5-112 nmol kg-1) increased the release of acetylcholine from the exposed parietal cortex of freely moving, morphine-tolerant guinea pigs. This increase was not additive and was prevented by prazosin (35.8 nmol kg-1), suggesting the involvement of alpha-1 receptors. At high doses (374 nmol kg-1 or more) clonidine inhibited acetylcholine release through alpha-2 receptors, as it did in naive animals at 7.5 nmol kg-1. Clonidine (374 nmol kg-1) and prazosin (35.8 nmol kg-1) reduced the objective signs of naloxone-precipitated withdrawal. Electrical stimulation of the locus ceruleus or naloxone treatment reduced the release of γ-aminobutyric acid (GABA) from the exposed parietal cortex of morphine-tolerant guinea pigs. This reduction was not additive and was prevented by idazoxan (84 nmol ka-1), suggesting the involvement of alpha-2 receptors. Clonidine (7.5 nmol kg-1), too, reduced the release ...