TY - JOUR T1 - Changes in cortical acetylcholine and gamma-aminobutyric acid outflow during morphine withdrawal involve alpha-1 and alpha-2 receptors. JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 682 LP - 687 VL - 250 IS - 2 AU - L Beani AU - S Tanganelli AU - T Antonelli AU - M Simonato AU - P Spalluto AU - C Tomasini AU - C Bianchi Y1 - 1989/08/01 UR - http://jpet.aspetjournals.org/content/250/2/682.abstract N2 - Naloxone (0.3-9 mumol 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 gamma-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 kg-1), suggesting the involvement of alpha-2 receptors. Clonidine (7.5 nmol kg-1), too, reduced the release of GABA in morphine-tolerant animals. However, when tested jointly with naloxone, clonidine (7.5-112 nmol kg-1) induced alpha-1-mediated facilitation of GABA release (like that elicited in naive animals at 112-374 nmol kg-1) leaving the signs of withdrawal unchanged. This points to the stimulation of alpha-1 receptors highly responsive to this agonist (but not to locus ceruleus stimulation) during naloxone-precipitated withdrawal. In conclusion, chronic morphine treatment modifies the alpha-1- and alpha-2-mediated control of GABA and acetylcholine neurons.(ABSTRACT TRUNCATED AT 250 WORDS) ER -