Various seizure activities following gamma-hydroxybutyrate

Winters, Wendell D.; Spooner, Charles E.

doi:10.1016/0028-3908(65)90034-1

Cited by 67 publications

(22 citation statements)

References 4 publications

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“…, 1983). Although burst suppression activity in the EEG is expected with the doses used in the present and the former studies (Winters and Spooner, 1965;Snead et aI., 1976;Wolfson et aI. , 1977), it was not accompanied by increased local glucose utilization, which occurs with seizure activity (Collins, 1976;Collins et aI.…”

Section: Discussionsupporting

confidence: 42%

Influence of γ-Hydroxybutyrate on the Relationship between Local Cerebral Glucose Utilization and Local Cerebral Blood Flow in the Rat Brain

Kuschinsky

Suda

Sokoloff

1985

J Cereb Blood Flow Metab

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Summary:The relationship between local cerebral glu cose utilization (LCGU) and local CBF (LCBF) was ex amined during the action of ,(-hydroxybutyrate (GHB) (900 mg/kg i. v.) in conscious rats. GHB induced dis crepant effects on blood flow and metabolism. LCGU was markedly depressed in all structures examined, whereas LCBF was differently affected in that no related changes were observed. Global glucose utilization was markedly depressed ( -51%), whereas global blood flowThe close correlation between metabolism and blood flow in the brain has recently been assessed by direct measurement of local cerebral glucose uti lization (LCGU) and local CBF (LCBF) in a variety of cerebral structures (Sokoloff, 1978;Kuschinsky et al., 1981; McCulloch et al., 1982a;Nakai et al., 1983). The mechanism that mediates this relation ship is not yet understood. Numerous studies have been carried out to elucidate the mechanism of the hyperemia that accompanies functional activation of the brain. Under these conditions, hyperemia ap pears to be triggered by the increased release of metabolically linked vasodilator substances. A number of candidates exist for such a local meta bolic control, e.g., H+, K +, adenosine, etc. [for references see Kuschinsky and Wahl (1978) and Kuschinsky (1982)], because their extravascular concentrations increase during functional activation to levels that induce vasodilation of pial arteries. Whereas such local metabolic factors seem to be mediators of hyperemia induced by acute functional Received June 19,1984; accepted October 17, 1984. Address correspondence and reprint requests to Prof. Dr. W. Kuschinsky at Department of Physiology, University of Bonn, Nussallee 11, 0-5300 Bonn 1, F.R. G, Abbreviations used: GHB, -y-hydroxybutyrate; LCBF, local CB F; LCGU , local cerebral glucose utilization. 58was not significantly altered. The marked dissociation be tween the changes in global glucose utilization and global blood flow induced by GHB is reflected only to a minor degree in the local values inasmuch as the correlation between LCGU and LCBF was only slightly weakened and its heterogeneity was increased. Key Words: 2-Deox yglucose-Iodoantipyrine-Local blood flow -Local coupling-Local metabolism-Rat brain.activation, the question still remains as to whether these factors are also responsible for the heteroge neity of LCBF that under normal conditions is closely correlated with local metabolism (Sokoloff, 1978;Kuschinsky et al., 1981; McCulloch et al., 1982a;Nakai et al., 1983).To investigate this question, the influence of marked metabolic depression on the relationship between local cerebral metabolism and blood flow was examined. ,),-Hydroxybutyrate (GHB) was chosen as a metabolic depressant. It is a naturally occurring substance in mammalian brain (Bessman and Fishbein, 1963;Roth, 1970;Roth and Giarman, 1970). Its pharmacological effects have been re viewed recently (Snead, 1977). As shown earlier for ,),-butyrolactone (Wolfson et al., 1977), GHB in high doses apparently reduces global cerebral energy...

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Section: Discussionsupporting

confidence: 42%

Influence of γ-Hydroxybutyrate on the Relationship between Local Cerebral Glucose Utilization and Local Cerebral Blood Flow in the Rat Brain

Kuschinsky

Suda

Sokoloff

1985

J Cereb Blood Flow Metab

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“…There is also evidence that GHB fulfills the criteria of a neurotransmitter or -modulator (Hasli and Hasli, 1983;Maitre and Mandel, 1984). The ex ogenous administration of GHB induces a depres sion of consciousness that is reflected by charac teristic changes in the EEG resembling a state of nonconvulsant epilepsy (Winters and Spooner, 1965;Snead et at., 1976) . During the action of GHB, the cerebral glucose utilization is markedly reduced in the awake rat (Kuschinsky et aI., 1985).…”

mentioning

confidence: 99%

Effect of γ-Hydroxybutyrate on the Reactivity of Pial Arteries before and after Ischemia

Haller

Kuschinsky

Reimnitz

1986

J Cereb Blood Flow Metab

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Summary: The effect of "{-hydroxybutyrate (GHB) on the reactivity of pial arteries to local metabolic factors was tested in chloralose-anesthetized cats before or after a pe riod of transient ischemia induced by air embolism. The vascular reactions were determined during the perivas cular microapplication of artificial CSFs with in creasing concentrations of adenosine (10-11_ 10-3 M), H + (pH 5.1-7. 6), or K + (0-JO mM). During nonischemic conditions the pial arterial reactivity to adenosine and H+, but not to K +, was significantly increased by GHB (250 mg/kg i. v. ) when compared with the control reac tivity. After cerebral ischemia the reactivity to adenosine was abolished with and without the administration of GHB prior to air embolism. The reactivity to K + was 'Y-Hydroxybutyrate (GHB) is a naturally occur ring cerebral metabolite (Roth and Giarman, 1970;Walters and Roth, 1977) with an unknown physio logical role. Although the conversion of GHB to 'Y aminobutyrate appears to be possible (Vayer et aI., 1985), the relevance of this step is a matter of dis pute. There is also evidence that GHB fulfills the criteria of a neurotransmitter or -modulator (Hasli and Hasli, 1983;Maitre and Mandel, 1984). The ex ogenous administration of GHB induces a depres sion of consciousness that is reflected by charac teristic changes in the EEG resembling a state of nonconvulsant epilepsy (Winters and Spooner, 1965;Snead et at., 1976) . During the action of GHB, the cerebral glucose utilization is markedly reduced in the awake rat (Kuschinsky et aI., 1985). Address correspondence and reprint requests to Prof. Dr. w.Kuschinsky at Physiologisches Institut der Universitat, Nu f3allee II, D-5300 Bonn I, F.R.G.Abbreviation used: GHB, 'Y-hydroxybutyrate. 658partly preserved but not increased by GHB when com pared with previous results without GHB. In contrast GHB improved the postischemic reactivity to perivas cular H+ that had been found to be abolished in previous experiments without GHB. The perivascular microappli cation of GHB showed no influence of GHB on the vas cular diameter. An important finding of the present study is the demonstration of an increase in cerebrovascular re activity, which may give scope for therapeutic improve ment of the regulation of CBF in pathophysiological conditions. Key Words: Cerebral ischemia-,,{-Hydroxy butyrate -Metabolic factors -Microapplication tech nique-Protection-Vasoreactivity.by pharmacological doses of GHB might be ex plained by an altered reactivity of the cerebral vessels to local metabolic factors. If such an effect also exists at physiological concentrations of GHB, a physiological role of GHB could be to modulate the cerebrovascular reactivity to metabolic stimuli.To test the possibilities of a physiological or phar macological action of GHB on the vascular reac tivity, the responsiveness of pial arteries to adeno sine, H +, and K + was determined during the action of GHB. These three substances play a major role in the local regulation of CBF under physiological conditions (Kusc...

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“…The motor excitements caused by GHB such as muscular twitching and convulsion in mice, and myoclonic jerks and grand mal seizures in cats and humans have been reported by several investigators (5,6,19,20). In the present experiments, GBL was con firmed to produce convulsion and twitching in mice.…”

Section: Discussionmentioning

confidence: 88%

The Central Action of Gamma-Butyrolactone and Gamma-Hydroxybutyrate

et al. 1967

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gamma-Butyrolactone (GBL) and its hydrolysate, gamma-hydroxybutyrate (GHB) have been known to distribute physiologically in the brain (1) -7) have suggested that the central action of GHB is rather excitatory than inhibitory, because GHB causes catatonia-like or hallu cinogenic state and even grand mal seizures by large doses in cats. The problems here are whether both GBL and GHB have excitatory central effects, and whether the effects depend on the species difference by which the central action varies..The comparison of behavioral effects of GBL and GHB among mice, rats and rabbits in the present experiments demontrated more central inhibitory nature of GBL than GHB as well as some signes of central excitement by both drugs. In addition, the possible mechanism of central excitement by GBL in rabbits was discussed electroencephalogra phically in relation to the similar effects of pentobarbital sodium and pentylenetetrazol. METHODSThe animals used were about 500 dd-strain mice of either sex, 30 male rats of Wistar strain and about 50 albino rabbits of either sex. They except mice were housed in an individual cage allowing free access to a commercial diet and water at the room tempera ture of 22--!-2°C.GBL and sodium salt of GHB were kindly supplied from Ono Pharmaceutical Co.,Osaka. The drugs dissolved in saline were injected to mice and rats intraperitoneally in volume of 0.1 ml/10 g body weight. In the rabbis, 10 to 20% solution of either drug was injected into the marginal ear vein at the rate of 1 to 2 ml/min. Thereafter, the changes in spontaneous behaviors, reflex activities and responses to grasping the animal body, tail pinch and skin scratching were observed at least for 6 hours after the drug

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Various seizure activities following gamma-hydroxybutyrate

Cited by 67 publications

References 4 publications

Influence of γ-Hydroxybutyrate on the Relationship between Local Cerebral Glucose Utilization and Local Cerebral Blood Flow in the Rat Brain

Influence of γ-Hydroxybutyrate on the Relationship between Local Cerebral Glucose Utilization and Local Cerebral Blood Flow in the Rat Brain

Effect of γ-Hydroxybutyrate on the Reactivity of Pial Arteries before and after Ischemia

The Central Action of Gamma-Butyrolactone and Gamma-Hydroxybutyrate

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