Narcotic tolerance and dependence: lack of relationship with serotonin turnover in the brain

Serotonin turnover was measured in mouse brain by means of the conversion of radioactivity from labeled tryptophan into serotonin. Animals with a high degree of tolerance to and physical dependence on morphine did not differ from control mice.     

Alcohol preference in the rat: reduction following depletion of brain serotonin

Preference for ethyl alcohol was significantly reduced or totally abolished in rats given orally p-chlorophenylalanine, a tryptophan hydroxylase inhibitor that selectively depletes brain serotonin. Some aversion to alcohol was observed while p-chlorophenylalanine was administered, but the rats' rejection of alcohol was even more marked after the drug was discontinued. Oral administration of alpha-methyl-p-tyrosine, a tyrosine hydroxylase inhibitor that depletes brain catecholamines, slightly reduced selection of alcohol, but preference returned to normal as soon as alpha-methyl-p-tyrosine was terminated.     

Persistent increase in brain serotonin turnover after chronic administration of LSD in the rat

Lysergic acid diethylamide at doses of 20 micrograms per kilogram per day was administered orally to rats for I month. Eighteen hours after the final dose a 25 to 30 percent increase in the synthesis and turnover of serotonin was noted, as well as a moderate but significant increase in the concentration of tryptophan (18 percent) and serotonin (13 percent) in the brain.     

Autoradiographic imaging of phosphoinositide turnover in the brain

With [3H]cytidine as a precursor, phosphoinositide turnover can be localized in brain slices by selective autoradiography of the product [3H]cytidine diphosphate diacylglycerol, which is membrane-bound. In the cerebellum, glutamatergic stimulation elicits an increase of phosphoinositide turnover only in Purkinje cells and the molecular layer. In the hippocampus, both glutamatergic and muscarinic cholinergic stimulation increase phosphoinositide turnover, but with distinct localizations. Cholinergic stimulation affects CA1, CA3, CA4, and subiculum, whereas glutamatergic effects are restricted to the subiculum and CA3. Imaging phosphoinositide turnover in brain slices, which are amenable to electrophysiologic studies, will permit a dynamic localized analysis of regulation of this second messenger in response to synaptic stimulation of specific neuronal pathways.     

Evoked release of norepinephrine and serotonin from brain slices: inhibitoon by lithium

Slices of mammalian brain accumulate H(3)-norepinephrine and H(3)-serotonin when incubated in a physiologic medium containing these tritiated monoamines. When these tissues are subjected to mild electrical stimulation of short duration, which is associated with depolarization of nerve membranes, a striking increase in the rate of efflux of the exogenous labeled monoamines occurs. Stimulation-induced release of both labeled monoamines is diminished by the presence of lithium ions in the perfusing medium; related monovalent cations had no such effect. Evoked release from slices of brain from animals treated intraperitoneally with lithium chloride for 3 days was also reduced.     

Narcotic drugs: effects on the serotonin biosynthetic systems of the brain

The effects of short- and long-term administration of morphine on the activity of two measurable forms of rat brain tryptophan hydroxylase were studied. Morphine administration produced an immediate decrease and a longterm increase in the nerve ending (particulate) enzyme activity but did not change the cell body (soluble) enzyme activity. Cocaine administration demnonstrated a short-term decrcease in measurable nerve eniding enzyme activity that was due to the inhibition of the high affinity uptake (the Michaelis constant, K(m) is 10-(5) molar) of trytophan, the serotonin precursor. Cocaine did not aflect the low affinity uptake K(m) = 10-(5) molar) of tryptophan. Both the uptake of the precursor and the enizymiie activity appeared to be drug-sensitive regullatory processes in the biosynthlesis of serotonin.     

Effects of phenylalanine diet on brain serotonin in the rat

Hooded rats fed diets rich in phenylalanine showed poorer performance on the Hebb-Williams maze than controls, as well as decreased brain serotonin levels. There did not appear to be a causal relationship between these findings, and the findings do not appear to be attributable either to a generalized behavioral defect or to inadequate dietary intake.     

Sleep patterns of the monkey and brain serotonin concentration: effect of p-chlorophenylalanine

The amount of time that monkeys (Macaca mulatta) slept was reduced after they were given p-chlorophenylalanine, a selective depletor of serotonin in animal tissues. The time spent in the rapid eye movement stage of sleep was unchanged, but the time in other sleep stages decreased. Seven regions of the brain had a 31 to 46 percent decrease in serotonin content; the concentration of cerebellar serotonin increased by 44 percent.     

Norepinephrine pools in rat brain: differences in turnover rates and pathways of metabolism

The rate of disappearance of intracisternally administered [(3)H]norepinephrine from rat brain gradually declines as a multiphasic exponential function of time. Conversion to [(3)H]normetanephrine accounts for a larger fraction of the [(3)H]norepinephrine released in the brain shortly after its intracisternal injection than that released at later times. Pools of norepinephrine in the brain thus appear to differ in their turnover rates and pathways of metabolism. The pool of norepinephrine with a rapid rate of turnover and an appreciable conversion to normetanephrine, identified by the techniques reported here, may correspond to a pool of newly synthesized norepinephrine in the brain.     

Rapid light-induced decrease in pineal serotonin N-acetyltransferase activity

Light acting by way of the eye causes the dark-induced activity of serotonin N-acetyltransferase in the pineal gland of the rat to decrease with a halving time of about 3 minutes. This effect, which is one of the more rapid physiological changes known to occur in the activity of any enzyme that metabolizes biogenic amines, appears to explain the rapid increase in the concentration of pineal serotonin that is caused by light exposure at night.     

Long-term amphetamine treatment decreases brain serotonin metabolism: implications for theories of schizophrenia

Long-term amphetamine administration to cats (a mean of 8.75 milligrams per kilogram twice daily for 10 days) produced large decreases (40 to 67 percent in serotonin and its major metabolite, 5-hydroxyindoleacetic acid, in all brain regions examined. This treatment also produced several behaviors that are dependent on depressed central serotonergic neurotransmission, and which normally are elicited exclusively by hallucinogenic drugs. Short-term amphetamine administration (15 mg/kg) did not produce these behaviors and resulted in small decreases in brain serotonin and no change in 5-hydroxyindoleacetic acid. These data are discussed in the context of monoamine theories of schizophrenia.     

Attention reduction and suppressed direct-current potentials in the human brain

Distraction suppresses direct-current potentials (contingent negative variation) recorded from the human scalp. This reduction is accompanied by retarded reaction time. Contingent negative variation and reaction time appear to reflect a common process, attention.     

Ependymal cilia: distribution and activity in the adult human brain

Examination of 150 to 200 samples of the ependymal lining of the ventricles of nine adult human brains obtained 2(1/2) to 6 hours post-mortem revealed cilia in at least 20 separate sites in the four ventricular cavities. In seven of the brains ciliary motion was evident, and in two of these it was wide-spread and rapid. It seems likely that the adult human ventricular ependyma is ciliated throughout. Currents having distinct patterns are induced in the ventricles of animal brains by ciliary motion, and such currents probably exist in man. A local mechanism for the rapid movement of cerebrospinal fluid is therefore present.     

Norepinephrine turnover and metabolism in rat brain after long-term administration of imipramine

The rate of disappearance of intracisternally administered tritiated norepinephrine from rat brain is decreased after a single dose of the tricyclic antidepressant imipramine. During long-term administration of imipramine, however, the rate of disappearance of tritiated norepinephrine from brain gradually increases, and there is a concurrent decrease in the content of endogenous norepinephrine in brain. These findings may help to explain why antidepressant effects are observed clinically only after long-termn treatment with imipramine.     

A strong influence of serotonin axons on beta-adrenergic receptors in rat brain

The role of serotonin axons in modulating the norepinephrine neurotransmission system in rat brain was investigated. Selective lesions of the forebrain serotonergic system were made by injecting 5,7-dihydroxytryptamine into the midbrain raphe nuclei. Four to six weeks after the lesion, the uptake of 3H-labeled serotonin in the frontal cortex and the hippocampus was reduced by more than 90 percent, while neither the uptake of 3H-labeled norepinephrine nor the content of norepinephrine was affected in either tissue. The number of beta-adrenergic receptors, as measured by radioligand binding with 3H-labeled dihydroalprenolol, was increased in the frontal cortex and hippocampus of rats with lesions. Similarly, specific lesions of central serotonin axons produced by systemically administered p-chloramphetamine resulted in an increase in the binding of 3H-labeled dihydroalprenolol to beta-adrenergic receptors and in the production of adenosine 3',5'-monophosphate in response to isoproterenol. These results indicate that serotonin axons may regulate beta-adrenergic receptor number and function in brain.     

Fissioning in planarians: control by the brain

Reduced population densities lead to increased rates of fissioning in planarians whereas higher population densities suppress fissioning. This effect is not primarily due to mucus deposition or substances secreted into the water. Experiments are presented which show a system of population feedback control. In the presence of other planarians, the brain exerts an influence (probably neurohormonal) to suppress fissioning. This influence becomes attenuated with axial distance from the brain.     

Lysergic acid diethylamide: role in conversion of plasma tryptophan to brain serotonin (5-hydroxytryptamine)

Injections of D-lysergic acid diethylamide decrease the turnover rate of 5-hydroxytryptamine of rat brain, as measured from the conversion of (14)C-tryptophan into (14)C-5-hydroxytryptamine. The 2-bromolysergic acid diethylamide given in doses fivefold greater than those of lysergic acid diethylamide fails to change the rate of (14)C-tryptophan conversion into (14)C-5-hydroxytryptamine. The effect of D-lysergic acid diethylamide is discussed with regard to its action on brain serotonergic neurons and its psychotomimetic effects.     

Parkinson's disease: activity of L-dopa decarboxylase in discrete brain regions

The activity of L-dopa decarboxylase was greatly reduced in the striatum, less so in the hypothalamus, and unchanged in the cortex of brains of patients with Parkinson's disease. However, it appears that even in the striatum enough activity remained to allow for the formation of dopamine from L-dopa in patients treated with large doses of L-dopa.