Cortical acetylcholine release is increased and gamma-aminobutyric acid outflow is reduced during morphine withdrawal.
The effects of naloxone on acetylcholine (ACh) and gamma-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.
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002540:Cerebral Cortex / Q000378:metabolism*; D003975:Diazepam / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D008297:Male; D009021:Morphine Dependence / Q000378:metabolism*; D009270:Naloxone / Q000494:pharmacology; D012964:Sodium / Q000502:physiology; D013375:Substance Withdrawal Syndrome / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D009270:Naloxone; D005680:gamma-Aminobutyric Acid; D001285:Atropine; D012964:Sodium; D000109:Acetylcholine; D003975:Diazepam