Quasi-morphine withdrawal behaviour: indication for a specific involvement of the GABA-ergic nerve terminal compartment.
Wet-dog-shaking resembling morphine withdrawal behaviour can be evoked in rats by administration of dipropylacetate (DPA). It has been postulated that DPA elicits the withdrawal like behaviour through specifically inhibiting the GABA-degradation in nerve terminals. Inhibition of GABA-transaminase (GABA-T) by aminooxyacetic acid (AOAA) in other compartments of the brain would result in an inhibition of the stimulated GABA-release via feedback on autoreceptors and therefore suppress the DPA-evoked behaviour. This hypothesis has been tested using the GABA-T inhibitors gamma-acetylenic-GABA (GAG), gamma-vinyl-GABA (GVG) and ethanolamine-O-sulphate (EOS). Although GAG and AOAA were found to suppress the body shakes, both GVG and EOS had no effect. Both GAG and AOAA have possibly also effect on glutamate decarboxylase (GAD) whereas GVG and EOS did not affect this enzyme, suggesting a nerve terminal-specific effect on DPA-induced behaviour. GVG stimulated DPA-evoked body shakes after 36 and 60 h, when a specific GABA-increase in nerve terminals will be present.
D000818:Animals; D006801:Humans; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D013239:Stereotyped Behavior / Q000187:drug effects*; D013375:Substance Withdrawal Syndrome; D014635:Valproic Acid / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D005680:gamma-Aminobutyric Acid; D014635:Valproic Acid; D009020:Morphine