Effects of inhibitors of GABA-transaminase on hole-board exploration and on temperature. Relation with effects on quasi-morphine abstinence behaviour induced by sodium dipropylacetate.
Four inhibitors of gamma-aminobutyric acid transaminase (GABA-T) were investigated together with respect to their effects on hole-board exploration and temperature and the relation with effects on quasi-morphine-abstinence behaviour induced by dipropylacetate (DPA) in rats. Amino-oxyacetic acid (AOAA), gamma-acetylenic-GABA (GAG), gamma-vinyl-GABA (GVC) and ethanolamine-O-sulfate (EOS) were found to reduce hole-board exploration especially in the higher doses used, although the time-course of the effect was different for the compounds. For EOS and GVG the decrease in hole-board exploration paralleled a strong hypothermic effect. The compounds AOAA and GAG exerted a less and more transient hypothermic effect. However, the decrease in hole-board exploration did not fall in with this decrease in temperature. AOAA and GAG were found to decrease DPA-induced body shakes and locomotor activity, while GVG and EOS had no effect on body shakes and transient effects but opposite to each other, on locomotor activity. The efficacy of the GABA-T-inhibitors was measured biochemically, and the influence on the activity of glutamate decarboxylase (GAD) was also determined. AOAA and GAG were found to be strong inhibitors of GABA-T whereas the other two compounds were less efficient in the used doses. In addition AOAA and GAG influenced the activity of GAD strongly, while using GVG only a small decrease was found. The results suggest that the anti-quasi-withdrawal, the sedative and the hypothermic effects are not related to each other nor related to an effect on GABA-T. The suppressive effects on quasi-withdrawal body shakes, however, could be related to the inhibition of GAD and a hypothesis involving a compartmentalized action of DPA on GABA-metabolism has been proposed.
D000612:4-Aminobutyrate Transaminase / Q000032:analysis / Q000037:antagonists & inhibitors*; D000625:Aminooxyacetic Acid / Q000494:pharmacology; D000818:Animals; D001831:Body Temperature / Q000187:drug effects*; D004983:Ethanolamines / Q000494:pharmacology; D005106:Exploratory Behavior / Q000187:drug effects*; D005968:Glutamate Decarboxylase / Q000032:analysis; D008297:Male; D009020:Morphine / Q000009:adverse effects*; D051381:Rats; D013375:Substance Withdrawal Syndrome / Q000139:chemically induced*; D014635:Valproic Acid / Q000494:pharmacology*
D004983:Ethanolamines; D000625:Aminooxyacetic Acid; D014635:Valproic Acid; D009020:Morphine; C020619:ethanolamine O-sulfate; D000612:4-Aminobutyrate Transaminase; D005968:Glutamate Decarboxylase