Pharmacological evidence for a selective antidopaminergic action of gamma-hydroxybutyric acid

Abstract

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.

Neuropharmacologic correlates of deglutition: Lessons from fictive swallowing

“…Indeed, various substances applied here will evoke repetitive fictive swallowing at latencies < 1 min (see next section). In the case of intracerebroventficular injections [8,12,18], there is a wider range of potential target structures, because solutes introduced into the lateral ventricle are free to penetrate into various circumventricular nuclei before or after having been distributed by bulk flow in the cerebrospinal fluid.…”

“…The general approach used to study fictive swallowing has been to record electromyographic (EMG) activity from muscle groups that form the floor of the mouth cavity and discharge early in the buccopharyngeal stage of reflex swallowing [3,6,7,12]. Since the chief muscles concerned (anterior digastric, geniohyoid, mylohyoid, and hyoglossus) contract in an overlapping tight sequence [6] and are closely apposed, EMG monitoring in practice samples summated activity from several muscles owing to volume conduction of muscle action potentials and the common use of bipolar wire electrodes with relatively large tips.…”

“…In predictable fashion, agents capable of releasing catecholamines from neuronal storage pools stimulate deglutition, as exemplified by (+)-amphetamine [3,6,12,26] and meta-methoxyamphetamine [9][10][11]. Catecholaminergic stimulation was initially attributed solely to an action at dopamine receptors [3], on account of the excitant action of the direct dopmine receptor agonist, apomorphine, and the lack of action of D,L-threo-3,4-dihydroxyphenylserine, which can undergo direct conversion to noradrenaline [30].…”

“…For instance, while treatment with reserpine (an agent with catecholamine-depleting activity) completely abolishes spontaneous swallowing, inhibition of monoamine oxidase with iproniazid, harmaline, pargyline, nialamide, or tranylcypromine results in persistent stimulation of swallowing and also strongly potentiates the precursor amino acid for catecholamines, L-dopa, which by itself is only moderately effective in activating fictive swallowing [1,3,5,6,12].…”

“…As a result, a number of relevant studies discussed below have probably not received much attention from investigators interested in deglutition. For the purpose of this paper, and for the sake ofa unifed terminology, the term "fictive swallowing" will be considered equivalent with earlier tentative designations of the same phenomenon, such as "oral or suprahyoideal myoclonic twitch" [3] and "oropharyngeal myocloniform twitch activity" [5,12]. In technical terms, the activity recorded in the majority of reports would only correspond to the buccopharyngeal stage of swallowing, because an esophageal component was not always verified.…”