Intensification of the central serotoninergic processes as a possible determinant of the thymoleptic effect.

An immunohistochemical study of serotonin neuron development in the rat: Ascending pathways and terminal fields

Immunohistochemical study of the development of serotonergic neurons in the rat CNS.

http://www.jandersonthomson.com/wp-content/uploads/2009/10/Andrews_et_al_serotonin_upper2015_NBR-1.pdf

Is serotonin an upper or a downer? The evolution of the serotonergic system and its role in depression and the antidepressant response

The uptake and storage of L-[3H]norepinephrine at various stages of development was examined in homogenates of rat brain. For the adult animal, active uptake accounted for 80 per cent of the total uptake. At 14 days of gestation, no active uptake was demonstrable At 18 days of gestation, saturable uptake of L-[3H]norepinephrine with a Km of 3 × 10 −7m was first demonstrable; the Km value did not vary during subsequent development. The Vmax. of uptake increased five-fold between 18 days of gestation and 28 days postnatally, at which stage it was the same as the adult value. The development of saturable uptake paralleled but preceded the increase in endogenous norepinephrine. When homogenates were incubated with l-[3H]norepinephrine and subjected to centrifugation on linear sucrose gradients, there was a peak of tritium in the synaptosomal fractions; the magnitude of the peak increased with maturation of the brain. The increase in the peak of tritium paralleled the increase in particulate LDH activity and was distinct from the peak of MAO activity. Desipramine, a compound that blocks the initial uptake of norepinephrine, first exhibited inhibition of uptake at 19 days of gestation; the degree of inhibition did not vary during subsequent development. In contrast, reserpine, a compound which inhibits the intra-neuronal storage of norepinephrine, exhibited a progressive increase of inhibition with maturation of the brain at and subsequent to 19 days of gestation.

Development of the uptake and storage of L-( 3 H)norepinephrine in the rat brain

ALTHOUGH the role of 5-hydroxytryptamine (5-HT): in neurophysiology is still obscure, several lines of evidence indicate that this amine may be involved in neural mechanisms in mammals. In addition, it is well documented that 5-HT and several drugs known to alter the metabolism of 5-HT have lethal, teratogenic, and prolonged behavioural effects on developing mammals. PEPEU and GIARMAN (1962) found that the administration of 5-HT to pregnant rabbits resulted in death of the foetus at a time when the 5-HT level in the maternal blood had only doubled and at a dose which caused no change in the maternal arterial pressure. LINDSAY, POULSON and ROBSON (1963) and POULSON and ROBSON (1963) described toxic actions of 5-HT and monamine oxidase (MAO) inhibitors at all stages of pregnancy in mice. Teratogenic effects may be seen in surviving foetuses of female mice given single injections of 5-HT (25-100 mg/kg) early in pregnancy (POULSON, ROBSON and SULLIVAN, 1963). In addition, 5-HT metabolism is altered in the inherited metabolic disease phenylketonuria, and has been implicated as a contributing factor in the production of the mental defects which accompany this disorder (PARE, SANDLER and STACEY, 1957). Finally, recent evidence indicates a possible correlation between the level of brain 5-HT at birth and the extent of development of the newborn in several mammalian species. Animals such as the rat (KATO, 1960; NACHMIAS, 1960; KARKI, KUNTZMAN and BRODIE, 1962; SMITH, STACEY and YOUNG, 1962) and rabbit (KARKI et al., 1962; PEPEU and GIARMAN, 1962), which are poorly developed, possess low levels of cerebra1 5-HT at birth; whereas the guinea pig (KARKI et al., 1962; S ~ T H et al., 1962) and goat (PEPEU and GIARMAN, 1962) species which are well developed and competent at birth, possess levels of cerebral 5-HT which approach or, in the case of the goat, exceed the adult levels. M A 0 activity parallels the levels of 5-HT in these species (SHIMIZU and MORIKAWA, 1959; NACHMIAS, 1960; KARKI et al., 1962; TISSARI, 1963), while 5-hydroxytryptophan decarboxylase (5-HTPD) activity approaches adult levels in the brains of the newborn in all species studied (KARKI et al., 1962; PEPEU and GIARMAN, 1962; SMITH et al., 1962; TISSARI, 1963).

Schedule of appearance of 5-hydroxy-tryptamine (serotonin) and associated enzymes in the developing rat brain.

IN PREVIOUS articles, evidence has been cited from bioelectric and behavioural studies that allows one to infer a dichotomy in the function of the phylogenetic+ly old and new cortex (MACLEAN, 1954; MACLEAN et al., 195S-56). This dichotomy has important implications because it bears upon the distinctive attributes of emotional and intellectual behaviour. The ‘old’ cortex comprises the so-called archicortex and mesocortex. The archicortex and the greater part of the mesocortex are contained in the great limbic lobe which is found in the brains of all mammals. The “old” cortex and its associated nuclear structures constitute a functionally integrated system which may be appropriately referred to as the limbic system (MACLEAN, 1952). In a study of the effect of neuropharmacological agents on the bioelectrical activity of the brain it was found that, following the administration of reserpine, distinctive changes could be localized in the hippocampus (MACLEAN et al., 1955-56), a structure which contains the greater part of the archicortex and which has important connections with the hypothalamus. Corresponding, but less pronounced, changes could also be localized in the region of the posterior hypothalamus. Subsequently, with the publication of the findings of PLETSCHER, SHORE, and BRODIE (1956), it became apparent that the evolution of the electroencephalographic changes (MACLEAN et al., 1955-56) followed a time course strikingly similar to that of the depletion and restoration of 5-hydroxytryptamine (5-HT) in the brain which they found after administering large doses of reserpine to rabbits. Heretofore it has been claimed that the amount of 5-HT in the cerebral cortex is negligible compared with that in the hypothalamus (AMIN, CRAWFORD, and GADDUM, 1954; PAASONEN and VOGT, 1956). In view of the foregoing observations and the suggestion that 5-HT might be of neurophysiological importance (GADDUM, 1954; WOOLLEY and SHAW, 1954; BRODIE and SHORE, 1957), a study was made of the 5-HT content of the hippocampus and other cortical and subcortical structures of the limbic system. This communication reports the findings.

5-Hydroxytryptamine (serotonin, enteramine) content of structures of the limbic system.

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Schedule of appearance of 5-hydroxy-tryptamine (serotonin) and associated enzymes in the developing rat brain.

5-Hydroxytryptamine (serotonin, enteramine) content of structures of the limbic system.