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Biomedical subjects

A G Watts

Publications and source records attributed to A G Watts.

At least 37 records · Page 2Linked to original sources

Osmotic stimulation differentially affects cellular levels of corticotropin-releasing hormone and neurotensin/neuromedin N mRNAs in the lateral hypothalamic area and central nucleus of the amygdala.

To investigate the effects of osmotic stimulation on neural circuits concerned with non-neuroendocrine aspects of homeostatic regulation, the levels of the mRNAs coding for corticotropin-releasing hormone (CRH) and neurotensin/neuromedin N (NT/NMN) in the lateral hypothalamic area (LHA) and central nucleus of the amygdala (CEA) of animals given 2.5% saline to drink overnight were measured semiquantitatively using in situ hybridization. Overnight osmotic stimulation leads to converse effects on the levels of these two mRNAs in different anatomical regions; increased levels of both mRNAs are seen in the LHA, but levels decrease in the CEA. While a number of previous studies have shown that ppCRH mRNA in the paraventricular (PVH) and supraoptic (SO) nuclei of the hypothalamus may contribute to the neuroendocrine response to osmotic stimulation, the present results show that in response to osmotic stimulation neurons located outside the PVH and SO may also modulate their synthetic potential, not just for CRH but also NT/NMN. These results suggest that a physiological stimulus may modulate the levels of two peptides previously identified in circuits projecting from the forebrain to nuclei in the brainstem, and as such, CRH and NT/NMN may participate in the regulation by the forebrain of the autonomic and/or behavioral responses of the animal to dehydration. Furthermore, these data show that a particular stimulus has opposite effects on the level of both peptide mRNAs when expressed in two different cell groups, suggesting first, that these peptides may have more than one role in the response, and second, the existence and influence of differential control mechanisms.

Amygdala↗

Disturbance of fluid homeostasis leads to temporally and anatomically distinct responses in neuropeptide and tyrosine hydroxylase mRNA levels in the paraventricular and supraoptic nuclei of the rat.

The response of six mRNAs (for prepro-corticotropin-releasing hormone, prepro-enkephalin, prepro-vasoactive intestinal polypeptide/peptide histidine isoleucine, prepro-neurotensin/neuromedin N, prepro-cholecystokinin, and prepro-tyrosine hydroxylase) was measured in the hypothalamic paraventricular and supraoptic nuclei after increasing periods of osmotic stimulation caused by the replacement of regular drinking water with hypertonic saline (up to five days) or by forced dehydration (up to three days). In addition, hematocrits and concentrations of corticosterone were determined after the different periods of osmotic stimulation and correlated with the effects on the content of the various mRNAs. The temporal response of the mRNAs within the paraventricular and supraoptic nuclei to osmotic stimulation was different within the three compartments of these nuclei. First, in response to overnight osmotic stimulation, magnocellular neurosecretory neurons increased their mRNA content for two molecules (prepro-corticotropin-releasing hormone and tyrosine hydroxylase). As the stimulus was maintained over the next two to four days, these cells accumulated the mRNAs for at least three other peptides (cholecystokinin, vasoactive intestinal polypeptide/peptide histidine isoleucine and enkephalin). Second, the response of peptide-coding mRNAs in parvicellular neurosecretory neurons of the paraventricular nucleus appeared to be slower; no changes could be measured after overnight stimulation. However, after a further two- to four-days of continued osmotic stimulation, the content of the mRNA coding for corticotropin-releasing hormone markedly decreased while that for cholecystokinin increased. No change in the content of the mRNAs coding for prepro-vasoactive intestinal polypeptide/peptide histidine isoleucine, enkephalin, and prepro-neurotensin/neuromedin N could be seen at any time after osmotic stimulation in parvicellular neurosecretory neurons. Third, increases in the content of mRNA coding for corticotropin-releasing hormone in the parvicellular neurons that provide descending projections from the paraventricular nucleus could only be detected after longer periods of osmotic stimulation. The effect of osmotic stimulation on plasma corticosterone concentrations was quickly apparent; plasma corticosterone concentrations were significantly elevated on the first morning after the beginning of salt-loading, and demonstrated the rapid effects of osmotic stimulation on the mechanisms controlling corticosterone release. These results show that the synthetic capability of cells in all three compartments of the paraventricular and supraoptic nuclei are modified by osmotic stimulation over different time scales, thereby allowing differential modulation of the neuroendocrine, autonomic, and behavioral components of the animal's response to disturbances in fluid homeostasis.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Hypothalamic-pituitary-adrenal axis function in the Zucker obese rat.

The development of many endocrine, metabolic, and behavioral abnormalities characteristic of genetically obese Zucker rats is dependent upon the presence of glucocorticoids, the secretion of which is regulated by a neuroendocrine cascade initiated by hypothalamic release of CRF. Recent reports have inferred alterations in central CRF tone as a putative factor contributing to dysregulation of the pituitary-adrenal axis and of metabolic processes in this phenotype. In the current study the hypothalamic CRF system in Zucker lean (FA/?) and obese (fa/fa) phenotypes was functionally evaluated. Neither the stalk median eminence content of CRF or arginine vasopressin (AVP) nor hypothalamic levels of CRF or AVP mRNA differed in the lean and obese phenotypes. No phenotypic differences were observed in either basal or stimulated CRF release from hypothalamic tissue obtained from lean and obese rats. Furthermore, in intact rats the magnitude of pituitary-adrenal responses to various stressors was also similar between phenotypes. However, secretion of CRF and AVP into the hypophysial-portal circulation of obese rats was, respectively, 73% and 35% lower than that of the lean rats. Adrenalectomy was associated with a 3-fold elevation of hypophysial-portal CRF levels in obese rats compared to intact controls. Corticosterone infusion was more effective in suppressing portal CRF levels in adrenalectomized obese compared to adrenalectomized lean rats. Finally, neither CRF receptor number and affinity nor the magnitude of pituitary-adrenal responses to rat CRF challenge (1 micrograms, iv) differed between Zucker phenotypes. These observations lead us to infer that rats of the obese phenotype exhibit reduced hypothalamic CRF tone due to dysregulation of the HPA axis at a site proximal to the hypophysiotropic CRF system that mediates glucocorticoid feedback regulation.

Adrenalectomy↗

Cell-specific expression of mRNAs encoding Na+,K(+)-ATPase alpha- and beta-subunit isoforms within the rat central nervous system.

We have used in situ hybridization histochemistry to analyze the subcellular distribution of mRNAs encoding Na,K-ATPase alpha- and beta-subunit isoforms in the rat central nervous system. Substantial differences in the cell-specific pattern of expression were found for the genes encoding three isoforms of the alpha subunit. Transcripts of alpha 1-subunit gene were detected in virtually all cell types and structures examined. Expression of alpha 2-subunit mRNA was characteristic of glia, whereas alpha 3-subunit transcripts were predominant in neurons. Transcripts encoding the beta 1 subunit were detected in neurons, whereas beta 2-subunit mRNA expression was characteristic of glia. mRNA encoding both beta-subunit isoforms was present in choroidal epithelial cells. The distribution pattern of alpha- and beta-subunit mRNAs in structures throughout the central nervous system is consistent with the possibility of six structurally distinct Na+,K(+)-ATPase isoenzymes.

Animals↗

Ether anesthesia differentially affects the content of prepro-corticotropin-releasing hormone, prepro-neurotensin/neuromedin N and prepro-enkephalin mRNAs in the hypothalamic paraventricular nucleus of the rat.

The content of the mRNAs that code for prepro-corticotropin releasing hormone (ppCRH), prepro-neurotensin/neuromedin N (ppNT/NMN) and prepro-enkephalin (ppENK) was measured using in situ hybridization histochemistry in the various subdivisions of the hypothalamic paraventricular nucleus (PVH) 4 h after a bout of ether anesthesia. This treatment increased the content of ppENK mRNA only in a selected region of the dorsal medial parvicellular PVH (PVHmpd). PpNT/NMN mRNA was undetectable in the PVH of control animals, but hybridization was observed in the PVHmpd of anesthetized animals. The content of ppCRH mRNA was unchanged 4 h after ether aesthesia.

Anesthesia↗

Enkephalin mRNA production by cochlear and vestibular efferent neurons in the gerbil brainstem.

Preproenkephalin mRNA production by efferent neurons projecting to the gerbil inner ear was assessed using combined in situ hybridization and retrograde labeling with fluorescent tracers. Virtually all vestibular efferent neurons were positive for preproenkephalin mRNA. Of the cochlear efferents, one-half of the medial olivocochlear neurons were positive for enkephalin. All lateral olivocochlear neurons were negative for enkephalin. The results suggest that there are two, biochemically distinct subpopulations of medial olivocochlear efferents in the gerbil.

Animals↗

Preservation of mRNA during in situ hybridization in the cochlea.

Specific nucleic acid sequences can be identified within cells using in situ hybridization. Hybridization for mRNA can document the distribution and amount of specific gene transcripts. Decalcification protocols used for immunohistochemistry in the cochlea were evaluated for use with in situ mRNA hybridization. No loss of mRNA was detected following the use of decalcification solutions at 4 degrees C when paraformaldehyde was added to the EDTA solution. The primary determinant of mRNA preservation was paraformaldehyde.

Animals↗

Exertional intensities and energy requirements of technical mountaineering at moderate altitude.

The purpose of this study was to determine the exertional energy requirements of technical mountaineering at moderate altitude. Six subjects completed maximum graded exercise tests (MGXT) prior to a 7-day ice climbing seminar conducted in the North Cascade Range of the United States. Mean weight, percent body fat, and maximum oxygen uptake (VO2max) were 71.3 (+/- 15.1) kg, 11.7 (+/- 4.2) %, and 53.7 (+/- 5.4) ml.kg-1.min-1 respectively. Heartrates (HR) were recorded and averaged over 5-second to 1-minute intervals during selected mountaineering activities of the ice climbing seminar. Average and peak estimated VO2 (EstVO2) and estimated energy expenditure (EstEE) were calculated from HR utilizing regression equations generated from the MGXT results. Trail hiking with loads averaging 45% of individual body weight required an average EstVO2 of 21.8 (+/- 3.0) ml.kg-1.min-1 and average EstEE of 7.5 (+/- 1.9) kcal.min-1 over a 2.2 hr period. Mean peak EstVO2 was 37.4 (+/- 3.4) ml.kg-1.min-1 and mean peak EstEE was 13.4 (+/- 3.0) kcal.min-1 during this period. Technical ice climbing involving movement up and down a 12 m vertical height for a mean time of 14.3 (+/- 2.6) min required an average EstVO2 and EstEE of 25.7 (+/- 7.6) ml.kg-1.min-1 and 9.5 (+/- 3.4) kcal.min-1 respectively. Peak EstVO2 and EstEE means were 38.4 (+/- 7.7) ml.kg-1.min-1 and 14.6 (+/- 3.5) kcal.min-1. Two subjects were monitored during a 6-hour summit ascent on snow and ice from 1636 m to 3266 m. Means for average EstVO2 and EstEE were 21.6 (+/- 3.3) ml.kg-1.min-1 and 7.2 (+/- 0.8) kcal.min-1 respectively while peak EstVO2 and EstEE means were 38.0 (+/- 6.1) ml.kg-1.min-1 and 13.3 (+/- 1.6) kcal.min-1. The total EstEE was 3096.8 and 2485.4 kcal for these two subjects over the 6-hour ascent. The most experienced climber averaged 0.078 kcal.kg-1.min-1 and the least experienced subject averaged 0.105 kcal.kg-1.min-1 while climbing at identical paces over the same terrain. This indicates a possible experience factor which may increase climbing efficiency.

Adult↗

Diurnal variations in the content of preprocorticotropin-releasing hormone messenger ribonucleic acids in the hypothalamic paraventricular nucleus of rats of both sexes as measured by in situ hybridization.

The content of mRNA coding for the precursor of CRH in the hypothalamic paraventricular nucleus (PVH) was measured in intact male and estrogen-treated ovariectomized female rats at different times of the day using in situ hybridization histochemistry. Plasma corticosterone concentrations were measured in separate groups of animals at the same time points, with females showing higher levels than males at all times, and both sexes exhibiting the well characterized diurnal rhythm. There was a significant decrease (greater in females) in the content of prepro-CRH (ppCRH) mRNA between midday and midnight in rats of both sexes. Previous studies have demonstrated that the content of ppCRH mRNA in the PVH responds inversely to changes in the concentration of plasma corticosteroid in a concentration-dependent manner. The present study suggests that ppCRH mRNA in the PVH may respond in a similar way to fluctuating concentrations of plasma corticosterone throughout the day, and that although the exact mechanism remains to be elucidated, diurnal changes in the rate of CRH synthesis may be involved in the expression of diurnal rhythms within the hypothalamo-hypophysial-adrenal axis.

Animals↗

The effects of knife cuts in the sub-paraventricular zone of the female rat hypothalamus on oestrogen-induced diurnal surges of plasma prolactin and LH, and circadian wheel-running activity.

To investigate the role of suprachiasmatic efferent connections in the expression of diurnal hormone rhythms, the efferent pathway from the suprachiasmatic nucleus (the putative circadian generator in the rat) to the subparaventricular zone (the main terminal area of suprachiasmatic efferents) was disrupted using bilateral horizontal knife cuts in ovariectomized oestrogen-treated rats. The position of the knife cut was assessed by observing its effect on vasoactive intestinal polypeptide immunoreactivity (a marker for suprachiasmatic efferents into the sub-paraventricular zone). The size of both the diurnal plasma LH and prolactin surges was markedly and consistently reduced over the 3-week period following the lesion in animals with a total deafferentation of the subparaventricular zone, compared with sham-operated animals or lesioned animals with an intact subparaventricular zone. When lesioned animals were grouped according to the presence or absence of damage to the preoptic area, no significant differences were found in the sizes of the plasma hormone surges. When similar knife cuts were given to animals whose activity cycles were observed, no significant effects were noted in the ability of the animals to synchronize to a light/dark regime or to free-run in constant light conditions. These results suggest that the suprachiasmatic nucleus influences the diurnal surges of plasma LH and prolactin in oestrogen-treated ovariectomized rats, initially by an interaction with the subparaventricular zone and not by a direct influence on gonadotrophin-releasing hormone neurones or other more rostral structures.

Animals↗

Gonadal steroids influence neurophysin II distribution in the forebrain of normal and mutant mice.

The distribution of arginine vasopressin-associated neurophysin (neurophysin II) immunoreactivity was investigated in normal and mutant house mice during development and after various gonadal steroid manipulations. During postnatal development of normal mice dense networks of neurophysin II immunoreactivity in the lateral septal nucleus and lateral habenular nucleus appeared earlier in male than in female mice, with an adult pattern of immunoreactivity being attained by 8 weeks and 12 weeks of age, respectively. The neurophysin II immunoreactivity in the male was denser than that in female mice. After gonadectomy of adult normal mice there was a gradual loss of neurophysin II immunoreactivity in the lateral septum and lateral habenula over a period of 15 weeks. In hypogonadal mice, a mutant in which gonadal development is arrested postnatally due to a deficiency in hypothalamic gonadotrophin releasing hormone, no immunoreactive neurophysin II could be detected in the lateral septum or lateral habenula. A pattern of neurophysin II immunoreactivity similar to that in normal control mice was observed in hypogonadal mice which had been implanted for 4 weeks with silicone elastomer capsules containing testosterone or oestradiol-17 beta, but not 5 alpha-dihydrotestosterone or progesterone. Stimulation of gonadal development and endogenous steroid production in hypogonadal mice by third ventricular grafts of preoptic area tissue from normal neonatal animals also produced a normal pattern of neurophysin II immunoreactivity in the lateral septum and lateral habenula. In the androgen-insensitive testicular feminized mouse immunoreactive neurophysin II was undetectable in the lateral septum and lateral habenula. Treatment of testicular feminized mice with oestradiol-17 beta, but not progesterone, produced a normal pattern of neurophysin II immunoreactivity. The main immunohistological findings were confirmed by radioimmunoassay of tissue extracts which showed that the concentration of arginine vasopressin in lateral septum was far greater in normal males than females and was undetectable in hypogonadal mice; no oxytocin could be detected in the septum of normal or hypogonadal mice. These results show that the expression of neurophysin II immunoreactivity in the lateral septum and lateral habenula of the mouse brain is dependent on the presence of aromatizeable androgens or oestrogens.

Aging↗

Efferent projections of the suprachiasmatic nucleus: I. Studies using anterograde transport of Phaseolus vulgaris leucoagglutinin in the rat.

The efferent projections of the suprachiasmatic nucleus (SCh) in the rat hypothalamus have been reexamined with the anterograde tracer Phaseolus vulgaris leucoagglutinin (PHA-L), which displays labeled axons with the clarity of a Golgi impregnation. Fibers from the SCh can be divided into six pathways for descriptive purposes. By far the densest terminal field arising from cells in the SCh ends in a roughly comma-shaped zone between the SCh and paraventricular nucleus on the one hand and the periventricular nucleus and anterior hypothalamic area on the other. A few axons continue dorsally from this "subparaventricular zone" to pass through parvicellular parts of the paraventricular nucleus and the overlying midline thalamic nuclei to end in midrostrocaudal parts of the paraventricular nucleus of the thalamus, and a larger number continue caudally to end in the dorsomedial nucleus, dorsal parts of the cell-sparse zone surrounding the ventromedial nucleus, and the posterior hypothalamic area. The other five pathways all consist of relatively small numbers of fibers and give rise to relatively sparse terminal fields. The second pathway consists of rostrally directed fibers that end in ventral parts of the medial preoptic area and anteroventral periventricular nucleus. The third consists of anterodorsally oriented fibers that pass through the medial preoptic nucleus and adjacent regions to end ventrally in the intermediate lateral septal nucleus. The fourth consists of fibers just caudal to the third group that end in the preoptic continuation of the bed nucleus of the stria terminalis, as well as in the parataenial nucleus and rostral part of the paraventricular nucleus of the thalamus. The fifth consists of laterally directed fibers that course over the optic tract to end in the ventral lateral geniculate nucleus. And the sixth consists of fibers that course posteriorally through the anterior hypothalamic and retrochiasmatic areas to end in the cell-sparse zone between the arcuate nucleus and ventral parts of the ventromedial nucleus, as well as in adjacent parts of the lateral hypothalamic area. The distribution of projections labeled following PHA-L injections centered in the subparaventricular zone was also examined and was confirmed with retrograde tracer experiments (Watts and Swanson: J. Comp. Neurol. 258:230-252, '87). The results indicate that the subparaventricular zone projects to essentially the same regions as the SCh, only much more densely, and also sends fibers back to the SCh.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Efferent projections of the suprachiasmatic nucleus: II. Studies using retrograde transport of fluorescent dyes and simultaneous peptide immunohistochemistry in the rat.

In a previous study (Watts et al., '87) we reexamined the projections of the suprachiasmatic nucleus (SCh) with the PHA-L method and found that they could be divided conveniently into six groups of fibers. By far the densest projection ends just dorsal to the SCh in a comma-shaped region designated the "subparaventricular zone," although some fibers continue on through the paraventricular nucleus of the hypothalamus to end in the overlying midline thalamus, and others continue on to end in the dorsomedial nucleus, the region around the ventromedial nucleus, and the posterior hypothalamic area. Other relatively sparse projections from the SCh were also described to the preoptic region, lateral septal nucleus, parataenial and paraventricular nuclei of the thalamus, and ventral lateral geniculate nucleus. In addition, the same method was used to show that the subparaventricular zone projects in turn massively to these same regions, as well as back to the SCh itself and to the periaqueductal gray. The present series of experiments was designed to confirm these observations with retrograde tracer injections and to investigate the cellular and possible neurotransmitter organization of the major projections from the SCh and subparaventricular zone with a combined retrograde tracer-immunohistochemical method. For this, the distribution of neuronal cell bodies within the SCh that stain with antisera to vasopressin, vasoactive intestinal polypeptide (VIP), corticotropin-releasing factor, bombesin, substance P, neurotensin, somatostatin, thyrotropin-releasing hormone, and angiotensin II was described in detail first. Then the distribution of retrogradely labeled neurons that were also stained for one or another of these peptides was described after injections of true blue, or in some cases SITS, into the regions of the subparaventricular zone, the paraventricular and parataenial nuclei of the thalamus, the ventromedial nucleus, the dorsomedial nucleus, and the periaqueductal gray. The results confirm previous immunohistochemical and anterograde tracing studies and in addition indicate that cells in dorsal as well as ventral parts of the SCh project to each of the terminal fields examined, as do many cells in surrounding areas, including the subparaventricular zone. Our results also suggest that, at the very least, vasopressin-, VIP-, and neurotensin-stained cells in the SCh project to the subparaventricular zone, midline thalamus, and dorsomedial nucleus, and that the vasopressin and VIP-stained fiber systems are partially segregated at the level of the subparaventricular zone.(ABSTRACT TRUNCATED AT 400 WORDS)

Angiotensin II↗

Changes in catecholamine concentrations in the hypothalamus and region of the midbrain raphe in male and female rats during postnatal development.

To investigate possible sex differences in central catecholaminergic systems, the concentrations of dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) were measured by high-performance liquid chromatography with electrochemical detection in the hypothalamus-preoptic area (H-POA) and midbrain raphe (MR) region of male and female rats throughout postnatal development. Other than a small but significant sex difference in DA concentration in the MR at 36 h (higher in females), the results showed that there were no sex differences in the concentrations of DA or DOPAC at any age in either brain region. The developmental profiles of the concentrations of DA and DOPAC showed that DAergic systems in the H-POA are immature at birth, with concentrations increasing steadily until 80 days of age, but in the MR concentrations reach a maximum at 20 days of age; a situation which is perhaps a reflection of differing monoamine metabolism in the two areas.

3,4-Dihydroxyphenylacetic Acid↗

Effects of intravenously administered 6-hydroxydopamine on the content of monoamines in the median eminence and neurointermediate lobe of the rat.

The effects of intravenous administration of 6-hydroxydopamine (6-OHDA) on the content of catecholamines in the median eminence and neurointermediate lobe was studied in male rats. The results confirmed previous findings of a depletion of catecholamines in both regions as a result of this lesion, although the magnitude of the effect was less than that revealed by fluorescence histochemistry. Administration of desipramine before 6-OHDA injection produced a more specific lesion, depleting dopamine but leaving noradrenaline unaffected.

3,4-Dihydroxyphenylacetic Acid↗

Effects of progesterone on the pituitary responsiveness to, and priming effect of luteinizing hormone releasing hormone in female rats exposed to constant light.

We have investigated the role of progesterone in the mating-induced release of luteinizing hormone (LH) and ovulation in female rats exposed to a 60-day period of constant light (LL). Plasma LH and progesterone concentrations were increased after mating; plasma estradiol concentrations, although not increased after mating, were increased compared with the concentrations in female rats on light-dark (LD) exposure during diestrus, proestrus evening and estrus. Progesterone induced ovulation in about half the number of female rats exposed to long-term LL, and in these animals, there was a significant increase in pituitary responsiveness to luteinizing hormone releasing hormone (LHRH) 5 h after progesterone injection. The magnitude of the priming effect of LHRH was markedly increased 2 h after progesterone treatment. Treatment with sodium pentobarbitone (SP) 15 min before an injection of progesterone, blocked the increase in pituitary responsiveness to LHRH 5 h later, but treatment with SP 4 h before progesterone injection did not block the increase in the magnitude of the priming effect of LHRH. These results suggest that progesterone acts both at the brain and pituitary to facilitate LH release, and that the increase in plasma progesterone produced by mating is at least partly responsible for the LH surge induced by mating in LL rats.

Animals↗

Ovulatory function and retinal catecholamine concentrations in female rats with and without inherited retinal photoreceptor degeneration.

The timing of the critical period and LH surge during the afternoon of proestrus was unchanged in female rats with degenerated retinal photoreceptors (Hunter and Royal College of Surgeons strains), when compared to female rats with intact retinae (Piebald Virol Glaxo and Wistar strains). Both RCS and Wistar strains responded to constant light (LL) exposure by attaining persistent vaginal cornification at the same rate. In addition, both RCS and Wistar strains regained normal estrous cycles when moved from LL to control lighting (LD). Therefore, an intact retinal photoreceptor layer is not essential for normal ovulatory function. In addition, these results show that the effects of LL on gonadotrophin secretion are mediated through the brain and are not the result of retinal degeneration. Measurements of retinal concentrations of dopamine (DA) and its metabolite, 3,4-dihydroxyphenylacetic acid (Dopac), in Wistar and RCS rats showed that concentrations of both compounds were reduced by LL, and then increased back to control values when animals were moved back into LD. Although the magnitude of the changes in retinal concentrations of DA and Dopac was greater in Wistar than in RCS rats (possibly related to the degeneration which occurs in Wistar but not RCS rats), these results suggest that dopaminergic cells, probably within the amacrine cell population of the retina, respond to different light regimes, perhaps by changes in activity.

3,4-Dihydroxyphenylacetic Acid↗

Effects of 5-hydroxytryptamine uptake blockers on the concentration in brain of 5-hydroxytryptamine and 5-hydroxyindoleacetic acid in male rats, pro-oestrous rats and ovariectomized rats treated with oestrogen and progesterone.

The aim of this study was to determine the effect of 5-hydroxytryptamine (5-HT) uptake blockade on 5-HT turnover by measuring the concentrations of 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) in brain with the aid of high performance liquid chromatography and electrochemical detection. The indoleamines were measured in the anterior hypothalamus (AH), posterior hypothalamus (PH) and raphe nuclei 30 min after the i.v. injection of either alaproclate (30 mg/kg) or zimelidine (20 mg/kg). The effect of alaproclate was studied in male rats, pro-oestrous female rats, rats ovariectomized and injected s.c. with 20 micrograms oestradiol benzoate (OB) on dioestrus and at 12.00 h of the next day (presumptive pro-oestrus) with 2 mg progesterone (model 1) and rats ovariectomized 3-4 weeks before an s.c. injection of 20 micrograms OB followed 72 h later by an s.c. injection of 2 mg progesterone (model 2). Alaproclate caused a significant decrease in the 5-HIAA/5-HT ratio in the AH and PH of the brain of male rats, in the PH and raphe nuclei in pro-oestrous rats and model 1, and in the raphe nuclei alone in model 2. Zimelidine had no effect on the 5-HIAA/5-HT ratio in any area in model 2. In male rats the injection of parachlorophenylalanine produced a marked reduction in the brain concentrations of 5-HT and 5-HIAA, but the 5-HIAA/5-HT ratio was unchanged by a subsequent injection of alaproclate. None of the pharmacological agents affected significantly the brain concentrations of noradrenaline, dopamine or dihydroxyphenylacetic acid.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine↗