No increase of synthesis of (R)salsolinol in Parkinson's disease.
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Adult↗
Biomedical subjects
S S Baum
Publications and source records attributed to S S Baum.
Effect of kava extract and individual kavapyrones on neurotransmitter levels in the nucleus accumbens of rats.
1. Kavapyrones have well-known psychotropic properties. The most common actions of the extract are relaxation and euphoria, depending on the circumstances of ingestion, whereas higher doses cause sleepiness and skeletal muscle relaxation. Several other actions have been reported such as anticonvulsant properties, neuroprotection and analgesia. No interactions with neuroreceptors have yet been found that would explain the multiple actions. 2. To reveal neuronal functions affected by the kavapyrones the authors studied their actions on the mesolimbic reward system using in vivo microdialysis. 3. A small dose of kava extract (20 mg/kg body weight i.p.) caused changes in rat behaviour and concentrations of dopamine in the nucleus accumbens. Higher doses (120 mg/kg i.p.) increased the levels of dopamine. With respect to the individual compounds, D,L-kawain induced in low doses a decrease in dopamine levels and in higher amounts either an increase or no change in dopamine concentrations. Yangonin resulted in a decrease of dopamine levels to below the detection limit and desmethoxyyangonin in an increase of dopamine levels. Dihydrokawain, methysticin and dihydromethysticin did not produce any significant changes of dopamine levels. D,L-kawain caused a decrease in 5-HT concentrations. Some of the other kavapyrones affected 5-HT levels as well. 4. The results suggest that the relaxing and slightly euphoric actions may be caused by the activation of the mesolimbic dopaminergic neurones. Changes of the activity of 5-HT neurones could explain the sleep-inducing action.
3,4-Dihydroxyphenylacetic Acid↗
Harman-induced changes of extracellular concentrations of neurotransmitters in the nucleus accumbens of rats.
Several beta-carbolines, including harman, induce voluntary ethanol intake in rats. It is not clear yet which mechanisms cause these effects. One possibility is the stimulation of the mesolimbic reward system. In vivo microdialysis was used to investigate the effects of acute injections of harman (1-methyl-beta-carboline) on extraneuronal concentrations of dopamine and 5-hydroxytryptamine in the nucleus accumbens, which in part the mesolimbic reward system. Administration of harman (2.27 mumol/kg, intraperitoneal application) elicited an increase of the dopamine efflux by 72% which returned to basal levels after approximately 300 min. In contrast, administration of an intermediate dose of harman (13.65 mumol/kg, intraperitoneal application) caused a significant decrease in efflux, to 76% of basal levels. Still higher doses included again an increased extracellular dopamine concentration. This change was statistically significant in only a subgroup rats, possibly because individual animals reacted differently to the high doses. Extracellular 5-hydroxytryptamine in the nucleus accumbens was increased during the first 2 h after the administration of high doses (40.94 and 81.93 mumol/kg, intraperitoneal application). These findings indicate that harman affects the activity of mesolimbic dopaminergic neurons following a U-shaped dose-response relationship.
Animals↗
Influence of dopaminergic transmission on severity of withdrawal syndrome in alcoholism.
OBJECTIVE: Dysfunction of dopaminergic transmission has been suggested as influencing withdrawal syndrome in alcohol-dependent patients. Therefore, dopamine levels and sensitivity of dopamine receptors were correlated with the severity of withdrawal syndrome in 40 alcoholics. METHOD: Dopamine blood plasma levels and apomorphine-induced Growth Hormone (GH) release were measured on the first day of detoxification (Day 1) and after 8 days of abstinence (Day 8). Severity of withdrawal syndrome was assessed daily by the Clinical Institute Withdrawal Assessment (CIWA) score. In the 22 patients (out of the 40) treated by chlormethiazole, severity of withdrawal was measured by the required chlormethiazole dose. RESULTS: A positive correlation was found between dopamine levels on Day 1 and the total CIWA score and necessary chlormethiazole dose, respectively. Correlation with the CIWA score was even stronger when the sensitivity of post-synaptic dopamine receptors was taken into account. No significant correlation between dopamine levels on Day 8 and withdrawal syndrome was found. CONCLUSIONS: Our findings indicate an influence of dopaminergic transmission on withdrawal syndrome during early withdrawal.
Adult↗
Evidence for prolonged recovery of dopaminergic transmission after detoxification in alcoholics with poor treatment outcome.
It has been hypothesized that dysfunction of dopaminergic neurotransmission is involved in the pathogenesis of alcohol addiction. Therefore, peripheral dopamine levels, sensitivity of central dopamine receptors (apomorphine-induced Growth Hormone (GH) secretion), and the inhibitory efficacy of G-proteins on adenylyl cyclase activity (as an indicator for dopamine D2-receptor coupled second messenger mechanisms) were measured in 45 alcohol-dependent patients before and after detoxification and in 10 healthy controls. The time needed to adjust to abstinence conditions differed between patients with good and poor treatment outcome. In subsequent abstainers, effects of alcohol withdrawal were already found during the first 24 hours of abstinence (normalisation of GH response, increases in dopamine levels and the inhibitory efficacy of G-proteins). During the next 7 days of abstinence, no more significant changes were observed in the assessed variables. In subsequent relapsers, no significant effect of acute ethanol withdrawal on the same measures was found. However, at day 8 of abstinence, increases in apomorphine-induced GH secretion (towards normalisation), in dopamine plasma levels, and in the inhibitory efficacy of G-proteins (towards above-normal levels) were observed. This retarded adjustment of dopaminergic signal transduction seems to reflect the relapse risk of treatment nonresponders.
Adult↗
Norharman-induced changes of extracellular concentrations of dopamine in the nucleus accumbens of rats.
In vivo microdialysis was used to investigate the effects of acute injections of norharman on extraneuronal concentrations of dopamine (DA) in the nucleus accumbens of rats. Administration of norharman (2.44 and 43.97 mumol/kg, i.p.) elicited an increase of the DA efflux by 70% and 160% respectively which returned to basal levels after 120 and 160 min respectively. In contrast, administration of an intermediate dose of norharman (7.33 umol/kg, i.p.) elicited a significant decrease to 72% of basal level. These findings indicate that norharman alters the activity of mesolimbic dopaminergic neurons in an U-shape manner. The observations further suggest several receptor mechanisms mediating the effects of norharman.
Animals↗
Determination of total dopamine, R- and S-salsolinol in human plasma by cyclodextrin bonded-phase liquid chromatography with electrochemical detection.
A reliable and sensitive high-performance liquid chromatographic (HPLC) method is presented for the determination of total (free and conjugated) plasma dopamine and the enantiomers R- and S-salsolinol. Plasma is purified on two cartridges, containing primary and secondary amines and phenylboronic acid. Dopamine, R- and S-salsolinol are then separated by HPLC using a beta-cyclodextrin-OH phase column. The eluate is monitored electrochemically, without further purification nor derivatization. The method is suited for routine analysis. It allows the detection of total (free and conjugated) dopamine and R- and S-salsolinol in human plasma in concentrations as low as 0.02 ng/ml plasma. The sensitivity is sufficient to measure the naturally occurring levels of salsolinol.
Biogenic Amines↗
A program for teaching cardiac surgery patients.
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Anxiety↗