Cortical acetylcholine release is increased and GABA outflow is reduced during morphine withdrawal

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. The cortical efflux of ACh in chronically‐treated guinea‐pigs was about half of that of normal animals. GABA efflux was unaffected. 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. 1986 British Pharmacological Society