Pharmacological evidence for a selective antidopaminergic action of gamma-hydroxybutyric acid.
D-Amphetamine (Amph) and p-chloroamphetamine (PCA) induced dose-dependent increases in oropharyngeal myocloniform twitch activity (MTA) in rats anesthetized with urethane. In doses of 80-120 mg/kg, gamma-hydroxybutyric acid (GHB) blocked Amph-induced MTA. The blockade was readily surmountable. Pretreatment with reserpine markedly enhanced the myoclonigenic effect of Amph and rendered it insensitive blockade by GHB, 160 mg/kg. PCA and tryptamine also effectively stimulated MTA, but unlike Amph were antagonized by low doses of the serotonin (5-HT) antagonist methysergide. In doses which blocked Amph, GHB failed to antagonize the myoclonigenic effect of PCA. It is concluded that: (a) the actions of Amph and PCA on MTA is less sensitive to GHB blockade than DA-mediated MTA; and (c) the GHB-Amph antagonism may be of a functional nature, i.e. result from a depression of the firing activity of DA neurons produced by GHB. Since reserpinization abolished the GHB effect on Amph-induced MTA, the functional integrity of granular DA binding and releasing mechanisms appears to be a pre-requisite for the antagonism between GHB and Amph.
D000818:Animals; D003913:Dextroamphetamine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006885:Hydroxybutyrates / Q000494:pharmacology*; D008297:Male; D008784:Methysergide / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D051381:Rats; D011954:Receptors, Dopamine / Q000187:drug effects*; D012110:Reserpine / Q000494:pharmacology; D013997:Time Factors; D014363:Tryptamines / Q000037:antagonists & inhibitors / Q000494:pharmacology; D010133:p-Chloroamphetamine / Q000037:antagonists & inhibitors / Q000494:pharmacology
D006885:Hydroxybutyrates; D011954:Receptors, Dopamine; D014363:Tryptamines; D010133:p-Chloroamphetamine; D012110:Reserpine; D003913:Dextroamphetamine; D008784:Methysergide