Microdialysis Study of Modification of Hypothalamic Neurotransmitters in Streptozotocin-Diabetic Rats

Abstract: Neurochemical changes in the ventromedial hypothalamus (VMH) after a single intravenous injection of streptozotocin were examined, using in vivo brain microdialysis under free-moving conditions. Although streptozotocin-induced diabetes produced significant decreases in extracellular concentrations of noradrenaline (NA), serotonin (5-HT), and their metabolites in the VMH, the ratios of 3-methoxy-4-hydroxyphenylglycol/NA and 5-hydroxyindoleacetic acid (5-HIAA)/5-HT were increased. Experimental diabetes led to a pronounced increase in extracellular GABA, which correlated strongly with the decrease in dialysate levels of NA, and to a smaller extent with that of 5-HT. A modification of dopamine (DA) metabolism was induced in the VMH of diabetic rats, whereas there was no change in dialysate DA levels. Daily injections of insulin were able to restore their levels to normal in the areas tested in the microdialysis study. The equal increases in dialysate 5-HT and 5-HIAA and the better restoration of the 5-HIAA/5-HT ratio after insulin therapy indicate that serotonergic activity may depend on the levels of circulating insulin more than on noradrenergic activity. Circulating NA was reduced in streptozotocin-diabetic rats, suggesting that the diabetes-induced reduction in sympathetic activity is accompanied by decreases in NA, or 5-HT, or both, in the VMH.     

Ventricular Cerebrospinal Fluid Monoamine Transmitter and Metabolite Concentrations Reflect Human Brain Neurochemistry in Autopsy Cases

Concentrations of dopamine (DA), its metabolites 3-methoxytyramine and homovanillic acid (HVA), noradrenaline (NA), its metabolites normetanephrine (NM) and 3-methoxy-4-hydroxyphenylglycol (MHPG), 5-hydroxytryptamine (5-HT, serotonin), and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) were measured in 14 brain regions and in CSF from the third ventricle of 27 human autopsy cases. In addition, in six cases, lumbar CSF was obtained. Monoamine concentrations were determined by reversed-phase liquid chromatography with electrochemical detection. Ventricular/lumbar CSF ratios indicated persistence of rostrocaudal gradients for HVA and 5-HIAA post mortem. Ventricular CSF concentrations of DA and HVA correlated positively with striatal DA and HVA. CSF NA correlated positively with NA in hypothalamus, and CSF MHPG with levels of MHPG in hypothalamus, temporal cortex, and pons, whereas CSF NM concentration showed positive correlations with NM in striatum, pons, cingulate cortex, and olfactory tubercle. CSF 5-HT concentrations correlated positively with 5-HT in caudate nucleus, whereas the concentration of CSF 5-HIAA correlated to 5-HIAA levels in thalamus, hypothalamus, and the cortical areas. These data suggest a specific topographic origin for monoamine neurotransmitters and their metabolites in human ventricular CSF and support the contention that CSF measurements are useful indices of central monoaminergic activity in man.     

Two-way avoidance and acute shock stress induced alterations of regional noradrenergic, dopaminergic and serotonergic activity in Roman high- and low-avoidance rats

Various brain regions of male RHA/Verh and RLA/Verh rats were dissected out and deep-frozen immediately after 30 min in a shuttle box involving a) no shock (control), b) 40 inescapable shocks or c) 40 avoidable shocks. The RHA/Verh rats used in the "c" category exhibited about 80-85% learned avoidance. 5-HT, 5-HIAA, NA, MHPG-SO4, DA, DOPAC and HVA levels were subsequently measured in selected regions. NA levels were considerably reduced in the hypothalamus and pons/medulla of both selected lines of rats after acute shock stress, supporting the results of numerous studies which have indicated that NA turnover is nonspecifically increased by all types of stress, at least in those regions. An increase in cortical MHPG-SO4 and a reduction in hypothalamic 5-HT seen after avoidance learning also occurred after shock stress in RHA/Verh rats. Whereas RLA/Verh rats showed an increased metabolism of 5-HT in the hypothalamus and pons/medulla after shock stress, RHA/Verh rats showed the opposite response in the hypothalamus after the same treatment. A reduction in 5-HT metabolism was also evident in RHA/Verh rats, after avoidance learning, in the cortex, hippocampus and hypothalamus. These results indicated, pending further studies regarding, for example, possible genetic differences in tryptophan uptake and utilization, that 5-HT probably plays at least a modulatory role in the reaction to stress, and in avoidance behavior. That role may be either active or passive, depending upon the emotional status of the subjects. In regard to the DA responses measured in striatum and hypothalamus of the two rat lines, some divergent inter-treatment tendencies, as well as some similarities, were seen in DA metabolism in both regions, but almost none of the differences were significant.     

Stress-Related Changes in Cerebral Catecholamine and Indoleamine Metabolism: Lack of Effect of Adrenalectomy and Corticosterone

The concentrations of catecholamine and indoleamine metabolites were measured in intact and adrenalectomized mice to determine whether adrenal hormones mediate or modulate the stress-induced responses. Thirty minutes of footshock resulted in significant increases of the ratios of the dopamine (DA) catabolite, dihydroxyphenylacetic acid (DOPAC), to DA in prefrontal cortex, nucleus accumbens, striatum, hypothalamus, and brainstem, and of homovanillic (HVA)/DA ratios in nucleus accumbens, striatum, amygdala, and hypothalamus. Ratios of 3-methoxy-4-hydroxyphenylethyleneglycol to norepinephrine (NE) were also increased in prefrontal cortex, nucleus accumbens, septum, amygdala, hypothalamus, hippocampus, and brainstem. The concentration of NE was decreased in amygdala. 5-Hydroxyindoleacetic acid (5-HIAA)/5-hydroxytryptamine (5-HT, serotonin) ratios and free tryptophan were also increased in every brain region. Very similar data were obtained from mice restrained for 30 min. Adrenalectomy resulted in increased HVA/DA ratios in prefrontal cortex and striatum, and 5-HIAA/5-HT in septum. The stress-related changes were largely similar in adrenalectomized mice. Significant interactions between adrenalectomy and footshock treatment occurred in prefrontal cortical DOPAC/DA and hypothalamic NE which was depleted only in adrenalectomized mice, suggesting tendencies for these measures to be more responsive in adrenalectomized mice. Corticosterone administration (0.5-2.0 mg/kg s.c.) which resulted in plasma concentrations in the physiological range did not alter the concentrations of the cerebral metabolites measured in any region. We conclude that adrenal hormones do not mediate cerebral catecholamine or indoleamine metabolism in stress, although adrenalectomy may affect HVA and 5-HIAA metabolism, and there was a tendency for catecholamines to be more sensitive to stress in adrenalectomized animals.     

Effects of acute and prolonged naphthalene exposure on brain monoaminergic neurotransmitters in rainbow trout (Oncorhynchus mykiss)

We have shown previously that acute (1 to 6 h) and prolonged (1 to 5 days) exposure of rainbow trout to naphthalene resulted in decreased plasmatic cortisol and 17-beta-estradiol levels. In order to elucidate the mechanisms through which naphthalene might disrupt endocrine regulation, the present study investigated whether brain monoaminergic neurotransmitters are altered by the action of this polycyclic aromatic hydrocarbon. In a first experiment, immature rainbow trout were injected with vegetable oil alone or containing naphthalene (10 and 50 mg/kg, i.p.), and sacrificed 1, 3 and 6 h after treatment. In a second experiment, slow-coconut oil implants alone or containing naphthalene (doses of 10 and 50 mg/kg) were i.p. located and fish sacrificed 1, 3 and 5 days after treatment. Levels of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA) and noradrenaline (NA) were measured in several brain regions by HPLC. The results show that short-term naphthalene increases DA and 5-HT contents in hypothalamus and telencephalon, but differentially alter contents of the acid metabolites. Implants with naphthalene reduced DA content in hypothalamus and preoptic region but increased in telencephalon. 5-HT metabolism was decreased in hypothalamus, preoptic region, pituitary and brain stem after 3 to 6 days of treatment. In addition, the levels of NA were increased in hypothalamus and telencephalon after acute treatment and in hypothalamus and preoptic area after several days of exposure to naphthalene. These data suggest that brain neurotransmitter systems are sensitive to polycyclic aromatic hydrocarbons and could represent a target of the naphthalene-induced neuroendocrine disruption.     

Neurochemical studies on Indian Hypericum perforatum L

The effect of acute administration of 50% standardised ethanolic extract of Indian Hypericum perforatum (IHp) was studied on the rat brain concentrations of monoamines and their metabolites in five different brain regions, viz. hypothalamus, hippocampus, striatum, pons-medulla and frontal cortex by a HPLC technique. IHp extract was administered at the doses of 50 and 200 mg/kg, p.o. and the brain monoamines were assayed after 30 min of the treatment. IHp treatment significantly decreased the levels of serotonin (5-HT) and its metabolite 5-hydroxy indole acetic acid (5-HIAA) and 5-HT turnover in all the brain regions assayed. On the other hand, IHp treatment significantly augmented the levels of norepinephrine (NE) and its metabolite methylhydroxy phenyl glycol (MHPG) and NE turnover in all the brain regions studied. Similarly, the levels of dopamine (DA) were also significantly augmented in the hypothalamus, striatum and frontal cortex. Likewise, the levels of dihydroxyphenyl acetic acid (DOPAC), the major metabolite of DA, were also increased in these brain areas. Pharmacological studies with IHp extract have shown two major behavioural actions, namely, anxiolytic and antidepressant effects. The present findings tend to rationalise these observations, reduced 5-HT activity being consonant with anxiolytic and increased NA and DA activity being consonant with antidepressant action.     

Effects of DSP-4 on monoamine and monoamine metabolite levels and on beta adrenoceptor binding kinetics in rat brain at different times after administration

Effects of DSP-4 on noradrenaline (NA), 3-methoxy-4-hydroxyphenyl glycol (MHPG), serotonin (5-HT) and 5-hydroxyindole acetic acid (5-HIAA) levels and on beta adrenoceptor binding kinetics (Bmax and K_D) in rat hippocampus, cortex and hypothalamus were studied between 24 hours and 14 days after systemic administration. Beta adrenoceptor numbers in hippocampus and cortex, but not in hypothalamus, were significantly increased after DSP-4. No significant changes in K_D values were observed in hypothalamus, but significant increases in this parameter were measured in hippocampus and cortex. NA and MHPG levels were significantly decreased in all three brain regions, but MHPG/NA ratios were increased in hippocampus, decreased in cortex and unchanged in hypothalamus. Very prominent increases in 5-HIAA levels were observed in all three brain regions, but only at one day after DSP-4. The greatest increases in 5-HIAA levels occurred in the hippocampus, but this effect of DPS-4 appeared to be slightly diminished by pre-treatment with fluoxetine. In cortex and hippocampus 5-HT levels were slightly, but significantly decreased after DSP-4.     

Effects of naloxone-precipitated withdrawal after a single dose of morphine on catecholamine concentrations in guinea-pig brain

The effect of naloxone-precipitated withdrawal after acute morphine was studied on the concentrations of noradrenaline (NA), 4-hydroxy-3-methoxyphenylethyleneglycol (MHPG), dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), and on the metabolite/parent amine ratios MHPG/NA, DOPAC/DA and HVA/DA, in eight regions of the guineapig brain. Guinea-pigs were treated with a single dose of morphine sulphate (15 mg/kg s.c.) or saline (control) and 2h later with naloxone hydrochloride (15 mg/kg s.c.) to precipitate withdrawal. The animals were decapitated at 0.5 h or 1 h after naloxone injections and their brains analysed for monoamine concentrations by HPLC-ECD. At 0.5 h after naloxone-precipitated withdrawal NA and MHPG levels, and the MHPG/NA ratio, were increased in the hypothalamus, and the NA levels were increased in the hypothalamus, medulla/pons and cortex 1 h after naloxone. Naloxoneprecipitated withdrawal also produced increased DA metabolism in the cortex, midbrain and medulla 0.5 h later, and in the cortex, hypothalamus and striatum 1 h later. Hence naloxone-precipitated withdrawal from acute morphine treatment produced a complex pattern of increased synthesis and metabolism of NA and DA which varied over time and with the brain region examined.     

Brain monoamines are involved in mediating the action of neurohypophyseal peptide hormones on ethanol tolerance

Two doses (0.3 and 3 ng peptide/animal) of oxytocin (OXT) and lysine-8-vasopressin (LVP) were earlier found to inhibit the development of tolerance to the hypothermic effect of ethanol in mice upon icv. administration. In the present paper the possible central monoaminergic correlates of the behavioral data were investigated. In tolerant animals the steady-state level of noradrenaline (NA) was increased in the hypothalamus, as was that of dopamine (DA) in the medulla oblongata; the serotonin (5-HT) and DA levels were decreased in the striatum as compared to those in the non-tolerant control. In the peptide-pretreated animals the NA level was increased in the hypothalamus, the DA level in the striatum, and the 5-HT level in the hippocampus and striatum. Opposite changes were observed in the steady-state levels of the monoamines in the hippocampus and striatum as compared to those in the tolerant controls. The data suggest that the central monoamines may be involved in mediating the actions of neurohypophyseal peptides on ethanol tolerance.     

Distribution of catecholamines,serotonin, and their major metabolites in the rat cingulate,piriform-entorhinal,somatosensory, and visual cortex: A biochemical survey using high-performance liquid chromatography

The catecholamines noradrenline (NA), dopamine (DA), adrenaline (AD), the indoleamine 5-hydroxytryptamine (5-HT; serotonin), as well as some of their major metabolites were assayed by high-performance liquid chromatography (HPLC) with electrochemical detection, in four well-defined areas of the rat cerebral cortex: anterior cingulate (CIN;Cg1 and Cg3), piriform and entorhinal (PiEn), hind-limb primary somatosensory (SSC;HL) and primary visual (VIS; Oc1M and Oc1B). The concentrations of NA and that of its main metabolite 3-methoxy-4-hydroxyphenylglycol were highest in PiEn, had intermediate values in CIN and were lowest for SSC and VIS cortices. The DA levels were also highest in PiEn, intermediate in CIN, while the lowest values were in SSC and VIS cortices. The different DA/NA ratios support the hypothesis that they are indeed independent neurotransmitters. In addition, the levels of 3,4-dihydroxyphenylacetic acid, homovanillic acid and 3-methoxytyramine paralleled the distribution of DA, thus confirming the presence of release sites, even in regions in which the low levels of this catecholamine could be interpreted simply as the precursor of NA. Traces of AD were detected in all the regions examined. The 5-HT contents, as well as that of its precursor 5-hydroxy-I-tryptophan and that of its metabolite 5-hydroxyindole-3-acetic acid were also found to be non-homogenous, with the highest levels measured in the PiEn and CIN regions.     

Chronic Stress Increases Serotonin and Noradrenaline in Rat Brain and Sensitizes Their Responses to a Further Acute Stress

The effects of 1 h/day restraint in plastic tubes for 24 days on the levels of serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), tryptophan (TP), and noradrenaline (NA) in six regions of rat brain 20 h after the last restraint period were investigated. The levels of 5-HT, 5-HIAA, and NA but not TP increased in several regions. The effects of 1 h of immobilization on both control and chronically restrained rats were also studied. Immobilization per se did not alter brain 5-HT, 5-HIAA, and TP levels, but decreased NA in the pons plus medulla oblongata and hypothalamus. However, immobilization after chronic restraint decreased 5-HT, increased 5-HIAA, and decreased NA in most brain regions in comparison with values for the chronically restrained rats. We suggest that chronic restraint leads to compensatory increases of brain 5-HT and NA synthesis and sensitizes both monoaminergic systems to an additional acute stress. These changes may affect coping with stress demands.     

Changes of Biogenic Amines and Their Metabolites in Postmortem Brains from Patients with Alzheimer-Type Dementia

Noradrenaline (NA), 3,4-dihydroxyphenylethylamine (dopamine, DA), 5-hydroxytryptamine (serotonin, 5-HT), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA) were measured in 22 regions of postmortem brains from four histologically verified cases with Alzheimer-type dementia (ATD) and nine histologically normal controls. Compared with the controls, concentrations of 5-HT and 5-HIAA in the ATD brains were significantly reduced in nine regions (superior frontal gyrus, insula, cingulate gyrus, amygdala, putamen, medial and lateral segments of globus pallidus, substantia nigra, lateral nucleus of thalamus) and in eight regions (amygdala, substantia innominata, caudate, putamen, medial and lateral segments of globus pallidus, medial and lateral nuclei of thalamus), respectively. NA concentrations of the ATD brains were significantly reduced in six regions (cingulate gyrus, substantia innominata, putamen, hypothalamus, medial nucleus of thalamus, raphe area). In contrast, significant reductions of DA and HVA concentrations in the ATD brains were found only in putamen and amygdala, respectively. The 5-HIAA/5-HT ratio in the ATD brains decreased significantly in locus coeruleus, while the HVA/DA ratio increased significantly in putamen and medial segment of globus pallidus. These findings suggest that the serotonergic and noradrenergic systems are affected, while the dopaminergic system is relatively unaffected in ATD brains.     

Regional distribution of monoamines in the nucleus accumbens of the rat

Monoamine concentrations were low in the rostral area of the nucleus accumbens. Their distributions were not identical. Differences were observed in the medial area. DA concentrations were high in both medial and caudal areas. Noradrenaline (NA) and serotonin (5-HT) concentrations were considerably lower than the dopamine (DA) concentration. The NA concentration was highest in the caudal area of the nucleus accumbens and the (5-HT) concentration was highest in the ventrocaudal area. There was a rostrocaudal decrease in the 3,4-dihydroxyphenylacetic acid (DOPAC)/DA and 5-hydroxyindole-3-acetic acid (5-HIAA)/5-HT ratios. Uptake of [³H]DA and [¹⁴C]choline was lowest in the rostral area. The K⁺-stimulated release of [¹⁴C]acetylcholine (ACh) was also lowest rostrally, but there was no rostrocaudal difference in the K⁺-stimulated release of [³H]DA. These results provide further evidence of the heterogeneity of the nucleus accumbens.     

Post-mortem changes of neurotransmitter concentrations in the rat brain regions

Using High Performance Liquid Chromatography coupled with electrochemical detection the post-mortem stability of noradrenaline (NA), dopamine (DA), serotonin (5-HT) and 5-hydroxy indole acetic acid (5-HIAA) were examined in the rat hypothalamus, amygdala, cerebral cortex, cerebellum and corpus striatum over an 8 hour time period. Changes in concentrations of the different neurotransmitters were less than it might be expected. The significant changes were: a. A fall in NA levels in the cerebral cortex by 4 hours and in the hypothalamus at 8 hours. b. A reduction in DA concentrations in the corpus striatum at 8 hours but a two fold rise of levels in the hypothalamus at 1 and 2 hours. c. A four-fold increase in 5-HT concentrations in the amygdala throughout the 8 hours studied. The results indicate that for comparative studies on post-mortem brain tissue correction factors should be employed to take into account differential changes in the concentrations of the various neurotransmitters.     

Plant-Derived Neurotoxic Amino Acids (β-N-Oxalylamino-l-Alanine and β-N-Methylamino-l-Alanine): Effects on Central Monoamine Neurons

In the present study the subacute effects of beta-N-oxalylamino-L-alanine (BOAA) and beta-N-methylamino-L-alanine (BMAA) on CNS monoamine neurons in rats were investigated following intracisternal injections or local intracerebral administration into substantia nigra. In vitro effects of BOAA and BMAA on high-affinity synaptosomal uptake of dopamine (DA), noradrenaline (NA), and serotonin (5-HT) were also examined. Intracisternal administration of BMAA decreased NA levels in hypothalamus, whereas no effects were seen on DA or 5-HT levels. Following intranigral injections of BOAA, NA levels tended to decrease in several regions, whereas the DA levels and the levels of DA metabolites were unaffected in all regions analyzed. Loss of tyrosine hydroxylase (TH) immunoreactivity in the intranigral injection sites and the presence of TH-immunoreactive pyknotic neurons near the borders of the injection sites were observed following both BOAA and BMAA treatments. Furthermore, substance P-immunoreactive terminals in substantia nigra pars reticulata were also found to have disappeared within the lesioned area following either BOAA or BMAA injections. Incubations with both BOAA and BMAA (10(-5) M) reduced high-affinity [3H]NA uptake in cortical synaptosomes to 69% and 41% of controls, respectively, whereas the striatal high-affinity [3H]DA uptake and the cortical high-affinity [3H]5-HT uptake were unaffected by BOAA or BMAA. The results demonstrate that both BOAA and BMAA can affect central monoamine neurons, although the potency and specificity of these substances on monoamine neurons when administered acutely into cerebral tissue or liquor cerebri seem to be low. However, the in vitro studies indicate selective effects of both compounds on NA neurons in synaptosomal preparations.     

Influence of hypo- and hyperthyroidism on the turnover rate of noradrenaline, dopamine and serotonin in various rat cerebral structures]

The effect of chronic treatment with tyroxine (T4) or propylthiouracile (PTU) on the turnover of norepinephrine (NE), dopamine (DA) and 5-hydroxytryptamine (5-HT) has been studied in various areas of the rat brain (brain stem, hypothalamus, striatum and "rest of the brain"). The turnover of NE and DA was determined by the decay in endogenous levels after inhibition of tyrosine hydroxylase by alpha-methylparatyrosine and the turnover of 5-HT was evaluated by the initial accumulation of endogenous 5-HT after inhibition of monoamine oxydase by pargyline. T4 treatment accelerated the release of DA from the striatum but had no significant effects on NA release in the various cerebral areas : nevertheless the NE endogenous level was significantly reduced in the brain stem. PTU treatment delayed the release of DA and NA only from the "rest of the brain". Concerning 5-HT, the only significant variation was observed in the hypothalamus of PTU-treated rats and implied increased turnover. The possible relations between the changes in cerebral monoamines turnover and the behavioural alterations which are observed in thyroid disfunction are discussed.     

Rapid, concurrent analysis of dopamine, 5-hydroxytryptamine, their precursors and metabolites utilizing high performance liquid chromatography with electrochemical detection: analysis of brain tissue and cerebrospinal fluid

Assays capable of measuring picomole quantities of dopamine (DA), 5-hydroxytryptamine (5-HT), several of their precursors and metabolites concurrently within 25 minutes were developed utilizing high performance liquid chromatography with electrochemical detection (LCEC). Several parameters of the LCEC were altered in order to separate the compounds while maintaining a short assay time. The final LCEC systems demonstrated biological utility in that the DA metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), and the 5-HT metabolite 5-hydroxy-3-indoleacetic acid (5-HIAA) were detected in rat cerebrospinal fluid; in addition to these compounds, DA and 5-HT were measurable in the striatum, hypothalamus and median eminence of the rat brain. Pargyline decreased the concentrations of DOPAC, HVA and 5-HIAA and increased the 5-HT concentration in all three brain regions, and increased the DA concentration in the striatum. Probenecid increased all three acid metabolite concentrations in the hypothalamus and median eminence, while only the HVA and 5-HIAA concentrations were increased in the striatum. The DA and 5-HT concentrations were unaltered. The LCEC methods described in this paper should be useful in elucidating the mechanisms and roles of 5-HT and DA neurons in experimental paradigms of biological interest.     

Neurotransmitter Changes in Guinea-Pig Brain Regions Following Soman Intoxication

The effects of the organophosphate acetylcholinesterase (AChE) inhibitor soman (31.2 micrograms/kg s.c.) on guinea-pig brain AChE, transmitter, and metabolite levels were investigated. Concentrations of acetylcholine (ACh) and choline (Ch), noradrenaline (NA), dopamine (DA), 5-hydroxytryptamine (5-HT), and their metabolites, and six putative amino acid transmitters were determined concurrently in six brain regions. The brain AChE activity was maximally inhibited by 90%. The ACh content was elevated in most brain areas by 15 min, remaining at this level throughout the study. This increase reached statistical significance in the cortex, hippocampus, and striatum. The Ch level was significantly elevated in most areas by 60-120 min. In all regions, levels of NA were reduced, and levels of DA were maintained, but those of its metabolites increased. 5-HT levels were unchanged, but those of its metabolites showed a small increase. Changes in levels of amino acids were restricted to those areas where ACh levels were significantly raised: Aspartate levels fell, whereas gamma-aminobutyric acid levels rose. These findings are consistent with an initial increase in ACh content, resulting in secondary changes in DA and 5-HT turnover and release of NA and excitatory and inhibitory amino acid transmitters. This study can be used as a basis to investigate the effect of toxic agents and their treatments on the different transmitter systems.     

Rat brain monoamine and serotonin S2 receptor changes during pregnancy

The concentrations of noradrenaline (NA), dopamine (DA), serotonin (5-HT), and their metabolites were determined in 5 brain areas of non-pregnant, 15 and 20 day pregnant and 4 day post-partum rats. Striatal 5-HT content was significantly lower in 15 and 20 day pregnant rats than in estrous controls. A significant decrease in striatal and frontal cortex 5-hydroxyindole-3-acetic acid (5-HIAA) concentration was observed in 15 day pregnant rats. Significant increases in hypothalamic and hippocampal NA levels were observed at 4 days post-partum. Frontal cortex serotonin S2 receptorKd was reduced in 4 day post-partum rats. There was no significant change in S2 receptorB _max during pregnancy. Levels of progesterone were negatively correlated with striatal DA, homovanillic acid (HVA), 5-HT, and 5-HIAA levels, hypothalamic DA, hippocampal 5-HT, and frontal cortex 5-HIAA values as well as striatal HVA to DA, and HVA to 3,4-dihydroxyphenylacetic acid (DOPAC) ratios and amygdaloid HVA to DOPAC ratios. The limbic neurotransmitter changes might possibly contribute to mood changes which occur during pregnancy and post-partum.     

The characteristics of the change in the catecholamine content of the brain in inbred mouse strains under zoosocial stress]

Noradrenaline (NA) and dopamine (DA) contents in various brain regions and their dependence on genotype, determining predisposition to domination, were studied during 7 days after the formation of artificial micropopulations consisting of 6 male mice of different genotypes. Significant changes of NA level were found in the olfactory bulbs and in the medulla oblongata and of DA in the hypothalamus and the hippocampus. Genotypic differences in NA levels were found in the hypothalamus and in DA levels--in the hippocampus. Reactions of RT males predisposed to domination differed both in noradrenaline and DA systems of the brain from the reactions of the males genetically predisposed to subordinate type of behaviour. Interconnection between the amines content both inside and between catecholamine systems was revealed.