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The dopamine (DA) and serotonin (5-HT) neurotransmission systems are of fundamental importance for normal brain function and serve as targets for treatment of major neuropsychiatric disorders. Despite central interest for these neurotransmission systems in psychiatry research, little is known about the regulation of receptor and transporter density levels. This lack of knowledge obscures interpretation of differences in protein availability reported in psychiatric patients. In this study, we used positron emission tomography (PET) in a twin design to estimate the relative contribution of genetic and environmental factors, respectively, on dopaminergic and serotonergic markers in the living human brain. Eleven monozygotic and 10 dizygotic healthy male twin pairs were examined with PET and [11C]raclopride binding to the D2- and D3-dopamine receptor and [11C]WAY100635 binding to the serotonin 5-HT1Areceptor. Heritability, shared environmental effects and individual-specific non-shared effects were estimated for regional D2/3and 5-HT1Areceptor availability in projection areas. We found a major contribution of genetic factors (0.67) on individual variability in striatal D2/3receptor binding and a major contribution of environmental factors (pairwise shared and unique individual; 0.70–0.75) on neocortical 5-HT1Areceptor binding. Our findings indicate that individual variation in neuroreceptor availability in the adult brain is the end point of a nature–nurture interplay, and call for increased efforts to identify not only the genetic but also the environmental factors that influence neurotransmission in health and disease.

1. The mobilization of gastric mucosal histamine as reflected by changes in formation and content has been studied in guinea‐pigs on feeding and after injections of pentagastrin or 2‐deoxy‐D‐glucose. 2. Re‐feeding fasting guinea‐pigs as well as injections of pentagastrin or 2‐deoxy‐D‐glucose raised the rate of mucosal histamine formation; pentagastrin induced a fourfold rise. 3. Some properties of the enzyme catalysing the formation of histamine were examined. The results indicated that this enzyme is histidine decarboxylase, L‐histidine carboxy‐lyase, E.C. 4.1.1. 22. 4. The enzyme imidazole‐N‐methyl transferase, E.C. 2.1.1.8, which carries out methylation of the imidazole ring to yield 1‐methyl‐4‐(beta‐aminoethyl)imidazole (methylhistamine), was found in high amounts in the mucosa. The enzyme did not change upon stimulation of the mucosa. 5. The metabolism of histamine within the gastric mucosa is discussed in relationship to a suggested role of the amine in exciting acid secretion.

1. The urinary excretion of histamine, methylhistamine, putrescine, cadaverine, spermidine and spermine was examined before, during and after pregnancy in rats. 2. During the last third of undisturbed pregnancy a distinct and steep rise occurred in the excretion of all amines studied except spermine. The peak values were found a few days before the birth of the young. In spermidine excretion a second peak was observed one or two days after delivery. 3. Before and during the first 2 weeks of gestation on a molar basis putrescine excretion was the greatest one. During the last trimester histamine was excreted in the largest amount. 4. Under the influence of the diamine oxidase inhibitor aminoguanidine the general pattern of excretion of diamines and polyamines in pregnant rats remained essentially unchanged but the total amount excreted increased. Most conspicuous was the great elevation of urinary contents of putrescine and cadaverine.

1. Histidine decarboxylase and ornithine decarboxylase activities were determined in mouse kidney and liver during post‐natal development. 2. The content of histamine, putrescine, spermidine and spermine was examined in kidney and liver and in the urine of adult male and female mice. 3. Histamine formation by the kidney was high in both sexes when determined a few days after birth but decreased during weaning. Thereafter, a distinct sex difference was established in that in the female kidney the level of histidine decarboxylase rose several‐fold during adolescence while in the male the level was still further reduced. 4. Putrescine formation by mouse kidney was low in both sexes up to three weeks of age whereafter the amine formation in the male increased conspicuously whereas that of the female kidney remained low. 5. The observed sex differences in tissue enzyme activities were reflected in concomitant differences in the amount of the diamines excreted in the urine. 6. No correlation was found between the actual enzyme levels and the assayed tissue content of histamine, putrescine, spermidine and spermine. 7. Following gonadectomy, the activities of both decarboxylases were significantly altered. Ornithine decarboxylase activity of male kidney and histidine decarboxylase activity of female kidney were strikingly reduced. 8. In the mouse liver, the two decarboxylases displayed no changes comparable with that of the kidney during development.

In female rats, mammary carcinoma were induced by DMBA (7,12-dimethylbenz(α)anthracene) administration. The activities of histidine and ornithine decarboxylases and the concentrations of histamine, putrescine and polyamines were determined in tumour extracts and urine. In the tumour tissue, formation of histamine and putrescine took place at much higher rates than in normal mammary tissue. Administration of compound 48/80 in doses that mobilized about 70% of histamine contained in the ear failed to release histamine contained in the tumour; 48/80 also failed to produce histological signs of degranulation of the tumour mast cells. It thus appears that these cells are different from mast cells in most normal tissues, a distinction that calls for further study.

In adrenalectomized mice, cortisone inhibited histidine decarboxylase of the kidney in a dose-related manner. The effect of cortisone on ornithine decarboxylase was diphasic: small doses elevated, high doses inhibited.

Conclusions Further development of this technique will be the use of a fluorescence detection method developed bySidney Udenfriend [4]. This method is reported to make analysis of as little as 50 picomoles possible, that is increasing the sensitivity about 20 times.

Conclusion It appears that the rapid method elaborated byOkuyama andKobayashi |2| is not well suited as a measure of diamine oxidase activity in tissues.