Alcohol, sleep and cerebrospinal fluid changes in alcoholics: cyclic AMP and biogenic amine metabolites in CSF.

Relative to baseline, one day of alcohol ingestion by chronic alcoholics demonstrated significant increases in SWS, decreases in REM sleep and decreases in CSF levels of cyclic AMP and 5-HIAA.

The effects of alcohol on cyclic AMP in mouse brain.

Detailed analysis of the dose-response and time-course relationship of ethanol to changes in adenosine 3',5'-cyclic monophosphate (cAMP) content of mouse brain revealed several patterns of response, including both decreases and increases depending on brain area. Whole-brain cAMP content was decreased with ethanol injection at all doses (0.4-3.

5-Hydroxytryptophan: A method for monitoring human plasma content during clinical administration.

A method is described for the assay of 5-hydroxytryptophan (5-HTP) in human blood plasma following administration of the compound. The procedure involves extracting the amino acid into butanol, returning the 5-HTP to an aqueous phase, and separating it from other interfering 5-hydroxyindoles on a column of Dowex 50W-X4, a strong cation-exchange resin. The concentration of 5-HTP in the buffer eluate is determined spectrofluorometrically in 3 N HCl; 25 ng/ml plasma can be detected.

The tryptolines: effect of intraventricular administration on spontaneous motor activity of rats.

The pharmacologic properties of the tryptolines, hindered analogues of the tryptamines, were studied behaviorally in rats. Following intraventricular injections, it was found that spontaneous motor activity decreased markedly during the initial 25 mins when compared with saline. Since both the tryptolines and tryptamines have been shown to be inhibitors of 5-hydroxytryptamine uptake, it may be possible that these compounds are acting indirectly throught an effect on the serotonergic system.

Tryptoline inhibition of serotonin uptake in rat forebrain homogenates.

We have examined the effects of six tryptolines (tetrahydro-beta-carbolines) upon 5-hydroxytryptamine (5-HT) uptake into rat forebrain homogenates. All six were found to be competitive inhibitors of 5-HT uptake. 5-Hydroxytryptoline, the most potent inhibitor, had an inhibitor constant (Ki) of 0.

Dopamine synthesis in rat brain striatal synaptosomes. I. Correlations between veratridine-induced synthesis stimulation and endogenous dopamine release.

The effects of depolarizing concentrations of veratridine were studied to determine the degree to which dopamine synthesis stimulation was correlated with stimulated endogenous dopamine release in rat brain striatal synaptosomes. Incubations included cocaine and pargyline to prevent dopamine reuptake and metabolism, respectively. Veratridine produced a 44% increase in dopamine release in 10 minutes and a similar increase in synthesis rate.

Dopamine synthesis in rat brain striatal synaptosomes. II. Dibutyryl cyclic adenosine 3':5'-monophosphoric acid and 6-methyltetrahydropterine-induced synthesis increases without an increase in endogenous dopamine release.

The effects of N6, O2'-dibutyryl cyclic adenosine 3':5'-monophosphoric acid (dibutyryl cyclic AMP), DL-6-methyl-5, 6, 7, 8-tetrahydropterine (6-MPH4) and tyramine on dopamine synthesis and endogenous dopamine release in rat brain striatal synaptosomes have been examined. Dibutyryl cyclic AMP (1 mM) produced a 100% increase in dopamine synthesis but had no effect on endogenous dopamine release. Veratridine (75 muM) did not further stimulate dibutyryl cyclic AMP-treated tissue.

Taming effects of p-chlorophenylalanine on the aggressive behavior of septal rats.

Septal irritability and shock-induced aggression were suppressed by the administration of p-chlorophenylalanine (PCPA) to septal rats. The levels of septal irritability and shock-induced fighting were significantly lower in septal, PCPC-treated rats than in nontreated septal rats. Since both parameters of septal aggression were reduced by PCPA, and while PCPA has no effect on shock-induced fighting of unlesioned rats under similar parameters, it appears that both forms of aggression may function through a common neural mechanism.

Neurochemical studies in a mouse teratoma with neuroepithelial differentiation. Presence of cyclic AMP, serotonin and enzymes of the serotonergic, adrenergic and cholinergic systems.

A transplantable mouse testicular teratoma (OTT 6050) which displays a spectrum of neuroepithelial differentiation was evaluated biochemically for concentrations of cyclic AMP (cAMP), serotonin (5-HT), and enzymes involved in the metabolism of the biogenic amines and acetylcholine. These values were compared between teratomas with neuroepithelial differentiation as the major or minor component and brains of neonatal and adult mice of related strains. cAMP, 5-HT, tryptophan hydroxylase (TPH), aromatic amino acid decarboxylase (AADC) and monoamine oxidase (MAO) were present.

The use of 5-hydroxytryptophan in a child with Lesch-Nyhan syndrome.

The effects of 5-hydroxytryptophan (5-HTP), a serotonin precursor, were studied in a boy with the Lesch-Nyhan syndrome. During the course of drug treatment, self-mutilation, crying, sleep state architecture, serum dopamine B-hydroxylase (DBH), and cerebrospinal fluid levels of 5-hydroxyindolylacetic acid and homovanillic acid were studied. Treatment with 5-HTP failed to affect this child's biting behavior.

Stimulation of rat striatal tyrosine hydroxylase by phospholipids and adenosine-3',5'-monophosphate.

Rat striatal tyrosine hydroxylase is stimulated in vitro by various phospholipids. This stimulation was produced by a 3- to 4-fold increase in affinity for pteridine cofactor. No change in the Km for tyrosine was observed, The sedimentation pattern of tyrosine hydroxylase on linear sucrose gradients showed no indication of enzyme dissociation in the presence of lysolecithin at maximal stimulatory concentration.

Enzyme activity in sleep and sleep deprivation.

Liver tyrosine transaminase activity is low during the day when the rats are mostly asleep and high during the night when they are awake. When wakefulness was imposed for 8 hr during daylight on the day of the experiment and the rats were allowed to sleep for the following 3 hr during darkness, the tyrosine transaminase activity became high during the day and low at night. That this reversal in enzyme activity is not mediated by the pituitary-adrenal axis is demonstrated by the fact that in adrenalectomized rats tyrosine transaminase activity increased during the day in the sleep deprived rats.

Facilitated shock-induced aggression following antidepressive medication in the rat.

Rats were tested for changes in shock-induced fighting following treatment with antidepressants of both the dibenzazepine and monoamine oxidase inhibitor classes of drug. Rats were retested for shock-induced fighting 3, 4, and 5 days after initial injections of imipramine (10 mg/kg IP bid), or saline. All three dibenzazepine groups showed increased levels of shock-induced fighting (p less than 0-01).

Effect of benzodiazepine compounds on brain amine metabolism.

In mice, chlordiazepoxide, diazepam and flurazepam reduced 5-HT synthesis and metabolism in the teldiencephalon following an i.v. injection of 3H-tryptophan.