Cortical acetylcholine release is increased and γ-aminobutyric acid outflow is reduced during morphine withdrawal

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Abstract
1 The effects of naloxone on acetylcholine (ACh) and γ-aminobutyric acid (GABA) outflow from the cerebral cortex of freely moving, morphine-dependent guinea-pigs was studied. 2 The cortical efflux of ACh in chronically-treated guinea-pigs was about half of that of normal animals. GABA efflux was unaffected. 3 During opioid withdrawal precipitated by naloxone (0.1–10 mg kg−1, i.p.) the guinea-pigs showed jumping, hyperactivity and wet dog shakes, the intensity of which was directly related to the dose of naloxone. The withdrawal syndrome was accompanied by a dose-dependent increase in ACh release and reduction in GABA outflow; ACh release was increased by naloxone at doses lower (0.1–3 mg kg−1) than those acting on GABA efflux (1–10 mg kg−1). Atropine (10 mg kg−1) and diazepam (5 mg kg−1) did not prevent GABA and ACh changes.