Selective increase of brain dopamine induced by gamma-hydroxybutyrate

Gessa, Gian Luigi; Vargiu, L; Crabai, F; Boero, Giorgia; Caboni, F.; Camba, R

doi:10.1016/0024-3205(66)90261-x

Cited by 195 publications

(48 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Since y-hydroxybutyrate has been shown to have no effect on monoamine oxidase or catechol-O-methyl transferase (Gessa et al, 1966), the enzymes which metabolize DA in the brain, the increase in DOPAC during the first hour after treatment with GHB-Na might reflect an increased metabolism of DA to this acid. Thus the total amount of DA formed during this time would be larger than that indicated by the observed increase in the concentration of DA.…”

Section: Discusionmentioning

confidence: 99%

The effect of sodium γ‐hydroxybutyrate on the metabolism of dopamine in the brain

Hutchins

Rayevsky

Sharman

1972

British J Pharmacology

View full text Add to dashboard Cite

Summary1. Sodium gamma hydroxybutyrate (GHB-Na), when given to rats and mice, caused a sleep-like state and a fall in body temperature of about 10°C. 2. GHB-Na produced a dose-dependent increase in the concentration of dopamine (DA) in the brains of mice kept at an environmental temperature of 1820o C or 30-32o C. 3. The concentrations of 3,4-dihydroxyphenylacetic acid (DOPAC) and 4-hydroxy-3-methoxyphenylacetic acid (HVA), the metabolites of DA, were increased in the striatal tissues of rats and mice, after the administration of GHB-Na. However there was a delay of 60 mi before the concentration of HVA increased whereas there appeared to be little delay before the concentration of DOPAC increased.4. When GHB-Na was administered to reserpine-treated animals, no increase occurred in the concentration of dopamine in the brains of mice or rats, or of DOPAC in the rat brain. 5. Reserpine did not prevent the induction of the sleep-like state by GHB-Na. 6. The results presented suggest that the effect of GHB-Na in increasing the concentration of DA requires unimpaired storage mechanisms for the amine.

show abstract

Section: Discusionmentioning

confidence: 99%

The effect of sodium γ‐hydroxybutyrate on the metabolism of dopamine in the brain

Hutchins

Rayevsky

Sharman

1972

British J Pharmacology

View full text Add to dashboard Cite

show abstract

“…We have now extended our earlier findings to examine whether another GABA potentiating drug (pentobarbitone) will also confer protection and also investigated the effect of two compounds known to interfere with dopamine release in the brain, namely y-butyrolactone (Gessa et al, 1966;Anden et al, 1973) and ondansetron (Butler et al, 1988). The former inhibits dopamine release in the striatum (see for example Chrapusta et al, 1992), while the latter is a 5-HT3 antagonist (Butler et al, 1988) and inhibits dopamine release in the nucleus accumbens (Kilpatrick et al, 1987;Costall et al, 1987).…”

Section: Introductionmentioning

confidence: 96%

A study of the mechanism of MDMA (‘Ecstasy’)‐induced neurotoxicity of 5‐HT neurones using chlormethiazole, dizocilpine and other protective compounds

Colado

Green²

1994

British J Pharmacology

View full text Add to dashboard Cite

An investigation has been made in rats into the neurotoxic effect of the relatively selective 5‐hydroxytryptamine (5‐HT) neurotoxin, 3,4‐methylenedioxymethamphetamine (MDMA or ‘Ecstasy’) using chlormethiazole and dizocilpine, both known neuroprotective compounds and also γ‐butyro‐lactone, ondansetron and pentobarbitone. Administration of MDMA (20 mg kg−1, i.p.) resulted in a 50% loss of cortical and hippocampal 5‐HT and 5‐hydroxyindole acetic acid (5‐HIAA) 4 days later. This reflects the long term neurotoxic loss of 5‐HT that occurs. Injection of γ‐butyrolactone (GBL; 400 mg kg−1, i.p.) 5 min before and 55 min after the MDMA provided substantial protection. Pentobarbitone (25 mg kg−1, i.p.) using the same dose regime was also protective, but ondansetron (0.5 mg kg−1 or 0.1 mg kg−1, i.p.) was without effect. MDMA (20 mg kg−1) had no significant effect on striatal dopamine concentration 4 days later but did produce a small decrease in 3,4‐dihydroxyphenylacetic acid (DOPAC) content. There were few significant changes in rats given MDMA plus GBL, ondansetron or pentobarbitone. A single injection of MDMA (20 mg kg−1, i.p.) resulted in a greater than 80% depletion of 5‐HT in hippocampus and cortex 4 h later, reflecting the initial rapid release that had occurred. None of the neuroprotective compounds (chlormethiazole, 50 mg kg−1; dizocilpine, 1 mg kg−1; GBL, 400 mg kg−1; pentobarbitone, 25 mg kg−1) given 5 min before and 55 min after the MDMA injection, altered the degree of 5‐HT loss. Acute MDMA injection increased striatal dopamine content (28%) and decreased the DOPAC content. In general, administration of the drugs under investigation did not significantly alter these MDMA‐induced changes. Both chlormethiazole and GBL produced a greater increase in dopamine than MDMA alone, but this was apparently an additive effect to the action of either drug alone. The 5‐HT loss 4 h following administration of the neurotoxin p‐chloroamphetamine (2.5 mg kg−1, i.p.) was not affected by chlormethiazole or dizocilpine. p‐Chloroamphetamine did not appear to alter striatal dopamine metabolism. None of the protective drugs inhibited the initial 5‐HT loss following MDMA, rendering unlikely any proposal that they are protective because they inhibit 5‐HT release and the subsequent formation of a toxic indole derivative. All the protective compounds (unlike ondansetron) probably inhibit dopamine release in the striatum. Since the neurotoxic action of some substituted amphetamines is dependent on the integrity of nigro‐striatal neurones, this fact may go some way to explain the protective action of this diverse group of compounds.

show abstract

“…In the chloral hydrate anesthetized rat, both drugs are capable of reversibly suppressing impulse flow leading to a compensatory increase in DA levels in terminal field areas, including the dorsal and ventral striatum (Gessa et al 1966;Hillen and Noach 1971;Roth et al 1973;Shepard and Lehmann 1992). S(-)HA-966 is considerably more potent in this regard than either GHB or the R( ϩ ) enantiomer of HA-966, which also exhibits affinity for the glycine allosteric site on the N-methyl-D-aspartate (NMDA) receptor (Singh et al 1990).…”

mentioning

confidence: 99%

Pertussis Toxin Lesions of the Rat Substantia Nigra Block the Inhibitory Effects of the γ-Hydroxybutyrate Agent, S(-)HA-966 without Affecting the Basal Firing Properties of Dopamine Neurons

Shepard

Connelly

1999

Neuropsychopharmacology

View full text Add to dashboard Cite

show abstract

Selective increase of brain dopamine induced by gamma-hydroxybutyrate

Cited by 195 publications

References 5 publications

The effect of sodium γ‐hydroxybutyrate on the metabolism of dopamine in the brain

The effect of sodium γ‐hydroxybutyrate on the metabolism of dopamine in the brain

A study of the mechanism of MDMA (‘Ecstasy’)‐induced neurotoxicity of 5‐HT neurones using chlormethiazole, dizocilpine and other protective compounds

Pertussis Toxin Lesions of the Rat Substantia Nigra Block the Inhibitory Effects of the γ-Hydroxybutyrate Agent, S(-)HA-966 without Affecting the Basal Firing Properties of Dopamine Neurons

Contact Info

Product

Resources

About