Behavioral and physiological characteristics of nonagouti mutation in gray rats during selection for aggressiveness

The goal of this work was to find out to which degree the black coat color mutation nonagouti that appears in wild Norway rat in the course of breeding for the maintenance and enhancement of aggressiveness towards a human affects selected and other behavioral traits as well as stress reactivity and brain neurochemistry. Nonagouti rats displayed increased emotionality in the open-field and forced-swimming tests as compared to agouti animals, whereas there were no differences in anxiety estimated in the elevated plus-maze. Neither were there any differences in glucocorticoid reactions to a combined stressful procedure such as forced swimming. The dopamine content in the frontal cortex and striatum and noradrenaline content in the frontal cortex were increased in black rats as compared to gray rats. The result suggest that the nonagouti mutation in gray aggressive rats enhances the effects of selection for aggressiveness on some behavioral traits and brain catecholamine level.     

Stress-Induced Sensitization of Dopamine and Norepinephrine Efflux in Medial Prefrontal Cortex of the Rat

Abstract: We examined whether prior exposure to chronic cold (17–28 days, 5°C) alters basal or stress-evoked (30-min tail shock) catecholamine release in medial prefrontal cortex, nucleus accumbens, and striatum, using in vivo microdialysis. Basal norepinephrine (NE) concentrations in medial prefrontal cortex did not differ between chronically cold-exposed rats and naive control rats (2.7 ± 0.3 vs. 2.5 ± 0.2 pg/20 µl, respectively). Basal dopamine (DA) efflux in any of the brain regions was not significantly different between chronically cold-exposed rats and naive rats. However, a trend for lower basal DA efflux in the cold-exposed relative to naive rats was observed in medial prefrontal cortex (1.5 ± 0.2 vs. 2.2 ± 0.3 pg/20 µl, respectively), nucleus accumbens (3.7 ± 0.8 vs. 5.4 ± 0.9 pg/20 µl, respectively), and striatum (4.4 ± 0.5 vs. 7.2 ± 1.5 pg/20 µl, respectively). In medial prefrontal cortex of rats previously exposed to cold, tail shock elicited a greater increase from baseline in both DA and NE efflux relative to that measured in naive rats (DA, 2.3 ± 0.3 vs. 1.2 ± 0.1 pg, respectively; NE, 3.8 ± 0.4 vs. 1.4 ± 0.2 pg, respectively). However, in nucleus accumbens or striatum of rats previously exposed to cold, the stress-induced increase in DA efflux was not significantly different from that of naive rats (nucleus accumbens, 1.8 ± 0.7 vs. 1.5 ± 0.3 pg, respectively; striatum, 1.9 ± 0.4 vs. 2.6 ± 0.7 pg, respectively). Thus, both cortical NE projections and cortically projecting DA neurons sensitize after chronic exposure to cold. In contrast, subcortical DA projections do not sensitize under these conditions.     

Effects of ethanol on brain monoamine content of spontaneously hypertensive rats (SHR)

Spontaneously hypertensive rats (SHR) were administered either 2.4 g/kg ethanol or an isocaloric glucose daily for 4 weeks and the levels of norepinephrine (NE), epinephrine (EP), dopamine (DA), serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in different brain regions were determined. Results indicated a 3-fold increase in NE level in brain stem and hypothalamus and more than 2-fold increase in DA in corpus striatum in alcohol-treated rats as compared to controls. There was a significant increase in the level of DA in the corpus striatum but the levels in cerebral cortex, brain stem and hippocampus were decreased instead. Decreases in 5-HT levels were found in hypothalamus, brain stem, cortex and cerebellum of alcohol-treated brain as compared to untreated controls. These results indicate alterations of the biogenic amine contents in different regions of the SHR brain after chronic ethanol ingestion. Since stimulated release of biogenic amines in the SHR brain has been implicated in the regulation of blood pressure, changes due to ethanol ingestion may be a risk factor in hypertensive patients.     

Differential effects of DSP-4 administration on regional brain norepinephrine turnover in rats

The effects of DSP-4 on brain NE levels and turnover in rats were investigated in six brain regions: cortex, hippocampus, cerebellum, brainstem, hypothalamus and locus coeruleus. Administration of 50 mg/kg of DSP-4 significantly decreased NE levels in all brain regions; greatest reductions occurred in the cortex (86% decrease) and in the hippocampus (91% decrease). Doses of DSP-4 less than 50 mg/kg did not significantly lower NE levels in other brain regions, except within the cerebellum. Levels of the NE metabolite 3-methoxy, 4-hydroxyphenylethylene glycol sulfate (MHPG-S04) declined in parallel with those of NE, except within the brainstem and the locus coeruleus. NE turnover, expressed as the ratio of the MHPG-S04 concentration to that of NE, was higher in the cortex and hippocampus than other regions in control animals, and NE turnover significantly increased only in these two areas after the administration of 50 mg/kg of DSP-4 (p less than 0.01). There were no significant changes in the levels of dopamine and a significant decrease of serotonin only in the striatum. These results indicate that DSP-4 is a neurotoxin with a strong predilection for noradrenergic neurons, that its effects vary according to brain region and that its administration increases NE turnover in those brain regions showing the greatest depletion of NE.     

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.     

Effect of aging on monoamines and their metabolites in the rat brain

Concentrations of dopamine (DA), norepinephrine (NE), serotonin (5-HT) and their acid merabolites were assayed in specific brain areas of Wistar rats of various ages. DA and its metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) were significantly lower in striatum and mesolimbic areas of old (24 mos) rats than young adult (3 mos), but not mature (12 mos) rats. The decrease of homovanillic acid (HVA) was significant in mesolimbic areas but not in striatum. Neither cortical NE nor its metabolite methoxydroxyphenylglycol sulphate (MHPG-SO₄) were significantly changed by aging. 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) in the brainstem showed a tendency to a decrease and increase respectively in aged animals compared with young adults, but the differences were not statistically significant. However, the ratio of 5-HIAA to 5-HT concentrations was significantly higher in aged animals. The conclusion can be drawn that, in these brain areas, DA is more vulnerable to aging than NE and 5-HT, the metabolism of the latter being even enhanced.     

Prenatal Ethanol Exposure: Changes in Regional Brain Catecholamine Content Following Stress

Abstract: Previous studies have shown that fetal ethanol exposure (FEE) may have long-term effects on the function of catecholaminergic neurons in different regions of the CNS. The present study is the first to examine the effects of FEE on regional brain catecholamine responses following acute stress (a single 60-min restraint stress), repeated stress (single periods of restraint stress on 1, 5, or 10 consecutive days), and recovery from stress (recovery for up to 60 min in the home cage following a single 60-min period of restraint stress). Both male and female offspring from FEE, pair-fed (PF), and ad libitum-fed control (C) groups were tested in adulthood to determine catecholamine content in the cortex, hypothalamus, and hippocampus. A single period of restraint reduced cortical norepinephrine (NE) content in FEE and PF animals compared with that in the cortex of C animals, and reduced hypothalamic NE content in FEE female offspring below that found in animals in all other groups. In contrast, hippo-campal NE content was higher in FEE than in C animals following a single period of restraint; PF animals had intermediate levels of hippocampus NE and did not differ significantly from either FEE or C animals. Following repeated periods of restraint, cortical NE content was lower in FEE than in C animals; PF animals once again had intermediate levels of NE. Importantly, basal (non stressed) NE content did not differ among groups in any brain area examined. In addition, several significant changes in regional brain catecholaminergic responses to acute stress were observed in animals across all treatment groups. Females generally had significantly lower cortical NE levels than males following both single and multiple exposures to restraint. In addition, the cortical NE content decreased below non-stressed levels in all groups following a single restraint period, and remained significantly below basal levels during the 60-min recovery period, whereas the hypothalamic NE content was significantly decreased immediately following the restraint period but showed some recovery toward basal levels by 60 min. There were no significant changes over time in hippocampal NE level or in cortical or hypothalamic dopamine (DA) content following a single restraint stress. Following multiple periods of restraint, hippocampal NE levels were significantly increased and hypothalamic DA levels were significantly decreased in all animals compared with basal levels. These data suggest that the brain noradrenergic response to acute stress is particularly sensitive to the effects of FEE, and that with regard to the hypothalamus, male and female offspring were differentially affected. Furthermore, nutritional effects appear to play some role in mediating the changes in regional brain catecholamine content that are observed. In addition, stress effects on brain catecholamine content across all treatment groups were found to be both region and sex specific.     

Release of endogenous norepinephrine and dopamine from rat brain regions in vitro

Using radioenzymatic assay procedures, we have measured picomolar amounts of endogenous norepinephrine (NE) and dopamine (DA) released $\text{in vitro}$. The release of NE and DA in response to KCl stimulation was examined in 6 brain regions: cortex, hippocampus, hypothalamus, striatum, combined accumbens-olfactory tubercle, and substantia nigra. NE release was detectable in all regions except striatum. Amounts of NE released by 55mM KCl (expressed as % control) were: cortex (313%), hippocampus (227%), hypothalamus (225%), accumbens-tubercle (278%), s. nigra (155%). KCl stimulated release of DA was detected in 3 regions: striatum (414%), accumbenstubercle (282%), and hypothalamus (312%). DA was measurable in filtrates from the s. nigra but levels in control and KCl stimulated samples were equal. Release of NE and DA was also measured in 12 brain regions after incubation of tissue $\text{in vitro}$ with 10^?4M d-amphetamine sulfate. d-Amphetamine stimulated NE outflow when compared to controls in all regions examined. DA outflow was markedly increased in most regions, especially striatum (287%), hypothalamus (387%) and accumbens-tubercle (670%). d-Amphetamine doubled endogenous DA outflow from the s. nigra.     

Vesicular and Ganglionic Norepinephrine in the Rat: Progressive Increase with Age

This study analyzed dopamine (DA) and norepinephrine (NE) in the synaptic vesicles and cytoplasm of brains of rats of 2 months and 14 months. The data revealed a clear NE increase in the synaptic vesicles of the 14-month-old rats, contrasting with NE in the cytoplasmic fraction of the rat brain, which remained unchanged with age. Synaptic vesicles from different regions of rat brain, including those from the striatum, consistently exhibited higher NE than DA concentrations, suggesting that they are predominantly noradrenergic. In the brain, DA concentrations in vesicular and cytoplasmic fractions did not vary with age, whereas in the superior cervical ganglia DA and NE concentrations increased in the older rats. L-3,4-Dihydroxyphenylalanine administration significantly increased DA without affecting NE in the ganglia of rats of all ages. In the brain, such a treatment significantly raised DA only in the synaptic vesicles of the older rats, suggesting an increased facilitation of DA transport into the synaptic vesicles with age, which may account for the higher vesicular NE in the older rats.     

Dermal-epidermal interactions and the action of alleles at the agouti locus in the mouse

In the mouse, alleles at the agouti locus determine eumelanin or pheomelanin synthesis by the follicular melanocytes. Previous studies have identified the dermis as the site of action of these alleles. However, a recent investigation utilizing the yellow (A^y) allele suggested a possible role of the epidermis in the expression of agouti locus alleles. Using dermal-epidermal recombinations of embryonic skin of various agouti genotypes, the present investigation supports the role of both the dermis and epidermis. If nonagouti ($\text{a}\text{a}$) dermis is recombined with agouti ($\text{A}\text{A}$) epidermis, the resulting hairs are pigmented in the nonagouti pattern. The reciprocal recombination of agouti dermis and nonagouti epidermis results in hairs pigmented in the agouti pattern. The recombinations of yellow ($\text{A}{}^{\mathrm{y}}\text{a}$) dermis and agouti or extreme nonagouti ($\text{a}{}^{\mathrm{e}}\text{a}{}^{\mathrm{e}}$) epidermis result in hairs completely pigmented in the yellow pattern (pheomelanin). However, when extreme nonagouti or agouti dermis is recombined with yellow epidermis, the resulting hairs are completely pigmented with pheomelanin. Similar results occur in recombinations of “young” yellow epidermis (13 days) and “old” dermis (17 days) even though dermal papillae are present. The role of dermal-epidermal interactions in the expression of agouti alleles as well as possible explanations for the unique action of the yellow allele are discussed.     

Dermal-epidermal interactions and the site of action of the yellow (Ay) and nonagouti (a) coat color genes in the mouse

The alleles at the agouti locus in mice determine whether eumelanin or pheomelanin is synthesized by the follicular melanocytes. Previous studies have indicated the dermis as the site of action of the agouti alleles, while implying that the epidermis plays only a passive role. Using methods of dermal-epidermal recombinations of embryonic yellow (A^y) and nonagouti (a) mouse skin, the study reported here indicates that the epidermis, as well as the dermis, plays a role in the action of the agouti alleles. When yellow dermis is recombined with nonagouti epidermis, the hairs produced contain only pheomelanin, thus substantiating the role of the dermis. However, the reciprocal combination of nonagouti dermis and yellow epidermis also produces hairs containing pheomelanin, indicating a more important role for the epidermis. The role of the dermal-epidermal interactions in the action of the alleles at the agouti locus is discussed.     

THE EFFECT OF BROMOCRIPTINE ON RAT STRIATAL ADENYLATE CYCLASE AND RAT BRAIN MONOAMINE METABOLISM

In slices and homogenate from rat brain striatum bromocriptine in marked contrast to DA. NA and apomorphine. had no stimulatory effect on adenylate cyclase activity, but antagonised the stimulatory effects of both NA and DA. Bromocriptine (10 mg/kg s.c.) decreased the turnover of DA in striatum and limbic structures 3h after drug administration. However, an increase in the turnover of NA in the brain stem and that of 5-HT in the cortex was observed 4h following treatment with bromocriptine. Possible modes of action of bromocriptine are discussed.     

Locally Administered Low Nicotine-Induced Neurotransmitter Changes in Areas of Cognitive Function

The present study examined the effect of a low-dose of nicotine; below that one expects to be achieved from a single cigarette, on brain regional heterogeneity and sensitivity of catecholaminergic responses. 1 μM nicotine was infused into six brain areas via a microdialysis probe: the dorsal and ventral hippocampus, the medial temporal and prefrontal cortex, the basolateral amygdala, and the ventral tegmental area (VTA). The nicotine concentration in the brain tissue near the probe site was approximately 0.1 μM. Nicotine-induced increases and decreases could be noted in dopamine (DA), norepinephrine (NE), and serotonin (5HT) levels. In particular, DA and 5HT decreased in both hippocampal areas, while NE increased in the dorsal and decreased in the ventral hippocampus. In the cortical areas, DA and NE increased and 5HT was not significantly altered. In the amygdala all three neurotransmitters increased and in the VTA, all three decreased. Many of the nicotine-induced changes in neurotransmitter concentrations were reversed in the presence of atropine. Where nicotine induced decreases in DA and 5HT in the VTA, increases were observed in the presence of atropine. A similar reversal was seen with NE in the VTA and ventral hippocampus. In contrast, the increases in DA observed in the cortex and amygdala and the increases in NE observed in the cortex, amygdala and dorsal hippocampus were inhibited by the presence of atropine. 5HT was also significantly decreased in the amygdala and both cortical areas in the presence of atropine, where nicotine alone had no significant effect. We conclude, that at low doses, nicotine significantly alters the release of DA, NE, and 5HT – in some areas increasing, in others decreasing endogenous neurotransmitter levels. This data, in conjunction with previous experiments, indicates that the effects of nicotine are regionally heterogeneous and arise from both direct and indirect actions on various receptors and neurotransmitter systems and nicotine’s effects at low doses differ from that at higher doses. The changes in effects in the presence of atropine suggest that muscarinic acetylcholine receptors play a major role in nicotine’s actions on neurotransmitter systems.     

Local Influence of Endogenous Norepinephrine on Extracellular Dopamine in Rat Medial Prefrontal Cortex

Abstract: Noradrenergic and dopaminergic projections converge in the medial prefrontal cortex and there is evidence of an interaction between dopamine (DA) and norepinephrine (NE) terminals in this region. We have examined the influence of drugs known to alter extracellular NE on extracellular NE and DA in medial prefrontal cortex using in vivo microdialysis. Local application of the NE uptake inhibitor desipramine (1.0 µM) delivered through a microdialysis probe increased extracellular DA (+149%) as well as NE (+201%) in medial prefrontal cortex. Furthermore, desipramine potentiated the tail shock-induced increase in both extracellular DA (stress alone, +64%; stress + desipramine, +584%) and NE (stress alone, +55%; stress + desipramine, +443%). In contrast, local application of desipramine did not affect extracellular DA in striatum, indicating that this drug does not influence DA efflux directly. Local application of the α₂-adrenoceptor antagonist idazoxan (0.1 or 5.0 mM) increased extracellular NE and DA in medial prefrontal cortex. Conversely, the α₂-adrenoceptor agonist clonidine (0.2 mg/kg; i.p.) decreased extracellular NE and DA in medial prefrontal cortex. These results support the hypothesis that NE terminals in medial prefrontal cortex regulate extracellular DA in this region. This regulation may be achieved by mechanisms involving an action of NE on receptors that regulate DA release (heteroreceptor regulation) and/or transport of DA into noradrenergic terminals (heterotransporter regulation).     

Effects of unilateral labyrinthectomy on the norepinephrine content in forebrain and cerebellar structures of albino rats

Albino (Wistar) rats were used to investigate whether unilateral labyrinthectomy (UL) modified the concentration of norepinephrine (NE) as well as of dopamine (DA) and the corresponding metabolite 3, 4-dihydroxyphenylacetic acid (DOPAC) in different areas of the cerebral and the cerebellar cortex and the striatum. The results obtained in 38 rats submitted to UL were compared to those of 18 rats submitted to sham-operation. The animals were operated under sodium pentobarbital anesthesia and sacrificed 1.5, 3 and 6 h after surgery. All rats submitted to UL showed phenomena of deficit (1.5-3 h after the lesion) followed by partial vestibular compensation (3-6 h after the lesion). Significant changes in the content of NE were neither found in different areas of the cerebral and the cerebellar cortex, nor in the striatum of rats sacrificed 1.5 h after UL. Three h after the lesion a bilateral increase in the NE content occurred in all the explored areas of the cerebral cortex (i.e., frontal, parieto-temporal and occipital) and the cerebellar cortex (i.e., the vermis and flocculus), as well as in the striatum. This increase, however, was more prominent in the parieto-temporal areas of the neocortex of the intact side, in all the explored areas of the cerebellar cortex of that side, as well as in the striatum of the lesioned side. This asymmetric increase in NE content could not be attributed, at least exclusively, to a generalized activation of the noradrenergic LC nuclei of both sides, due to waking and/or stress which may occur after UL, but did rather depend on asymmetric changes in unit discharge of the vestibular nuclei projecting to the LC of both sides, following UL. In particular, the increased discharge of the vestibular nuclei of the intact side would lead to activation of noradrenergic neurons projecting particularly to the parieto-temporal cortex and the cerebellar cortex of the intact side, as well as to the striatum of the lesioned side. A bilateral increase in NE content was still observed in different areas of the cerebral and cerebellar cortex of rats sacrificed 6 h after UL. This increase, however, was of smaller entity than that observed in the same areas 3 h after UL and quite symmetric. The content of DA and its metabolite DOPAC decreased bilaterally in the striatum of rats sacrificed 1.5 h after UL. This effect was attributed to a reduced synthesis and release of DA, which probably resulted from a reduced facilitatory influence that the deafferented vestibular nuclei exert on the dopaminergic, nigrostriatal system of both sides, although mainly on the intact side. The corresponding values, however, bilaterally recovered to slightly increase with respect to the control values in rats sacrificed 3 and 6 h after UL. In these experiments the content of both DA and DOPAC remained symmetric on both sides after UL, in contrast with the bilateral but asymmetric increase in NE concentration observed in the same structure 3 h the lesion. The present results integrate and extend those of previous experiments showing that: 1) albino rats sacrificed 6 h after UL displayed an increased synthesis of NE, which affected particularly the LC of the intact side as well as the medial vestibular nuclei of both sides (21); and 2) the structures which showed an increased content of NE at given time intervals after UL also displayed an increase in the expression of the immediate early gene c-fos (cf. 16 for ref.). These findings suggest that bilateral but asymmetric activation of the noradrenergic LC neurons following UL may lead to an asymmetric increase in c-fos expression in several target structures, thus contributing to the plastic changes responsible for vestibular compensation. In conclusion, it appears that UL induces in several brain structures of albino rats a short-term increase in synthesis and release of NE. (ABSTRACT TRUNCATED)     

Regional Differences in 5-Hydroxytryptamine and Catecholamine Uptake in Primary Astrocyte Cultures

The uptake of 3H-labelled 5-hydroxytryptamine (5-HT, serotonin) norepinephrine ([3H]NE), and 3,4-dihydroxyphenylethylamine ([ 3H]dopamine, [3H]DA) was studied in primary astrocyte cultures prepared from the cerebral cortex, corpus striatum, and hippocampal regions of neonatal rat brain. Na+-dependent uptake showed marked regional differences. For [3H]5-HT the magnitude of uptake was corpus striatum greater than or equal to cerebral cortex greater than hippocampus, whereas for [3H]NE the order was hippocampus greater than corpus striatum greater than cerebral cortex. For [3H]DA, only the hippocampal cultures showed significant Na+-dependent uptake. [3H]5-HT uptake was specifically inhibited by 10(-7) M fluoxetine whereas [3H]NE uptake was preferentially inhibited by 10(-7) M desipramine. These results may reflect regional brain specialization and/or different developmental patterns of high affinity uptake of serotonin and catecholamines by astrocytes in situ.     

Alterations in Norepinephrine and Dopamine Content in Selected Brain Areas of Guinea Pigs Adapted to Simulated High Altitude

Abstract: The alterations in brain content of norepinephrine (NE) and dopamine (DA) were studied in guinea pigs adapted to simulated high altitude (hypobaric hypoxia) equivalent to 5500 meters. The animals were adapted for 46 days over a period of 82 days to a pressure of 375 mm Hg. The animals were then killed and the following brain parts dissected: cerebellum, neocortex, caudate head/basal forebrain, diencephalons/rhinencephalon, and brain stem. NE and DA content were analyzed by high pressure liquid chromatography with electrochemical detection by a technique described. Results showed a significant increase of NE and DA in neocortex; a significant increase of DA but not NE in caudate/basal forebrain, and a significant decrease of NE and not DA in diencephalons/rhinencephalon.     

贯叶连翘对应激大鼠生长和脑单胺类神经递质含量的影响

为探讨贯叶连翘对慢性应激大鼠生长和脑单胺类神经递质的影响,用15只大鼠设置对照组、应激组和贯叶连翘组3组实验。应激组和贯叶连翘组均进行7天的应激刺激后,贯叶连翘组灌胃贯叶连翘10d。实验结束后,取3组大鼠的脑组织,用高效液相色谱法测定高香草酸(HVA)、去甲肾上腺素(NE)、多巴胺(DA)和5-羟色胺(5-HT)的含量。结果表明,应激组大鼠日增重明显低于对照组;而贯叶连翘组大鼠的日增重明显高于应激组。应激组大鼠海马、纹状体和前额叶中的HVA、NE、DA和5-HT与对照组间均无显著差异。贯叶连翘组大鼠纹状体中的DA含量明显高于应激组;而前额叶中的DA则明显低于应激组。因此,贯叶连翘对慢性应激引起的大鼠生长受抑有缓解作用,对其脑内单胺类神经递质有部分调节作用。     

合欢花对慢性应激大鼠生长和脑单胺类神经递质含量的影响

为探讨合欢花对慢性应激大鼠生长和脑单胺类神经递质的影响,采用15只大鼠,设置了对照组、应激组和合欢花组3组实验。应激组和合欢花组均接受7天的应激刺激,之后合欢花组再灌胃合欢花10天。实验结束后,取3组大鼠的脑组织,用高效液相色谱法测定高香草酸(HVA)、去甲肾上腺素(NE)、多巴胺(DA)和5-羟色胺(5-HT)的含量。结果表明,应激组大鼠日增重显著低于对照组(P=0.011);而合欢花组大鼠的日增重极显著高于应激组(P=0.002)。应激组大鼠海马、纹状体和前额叶中的HVA含量与对照组相比,虽有升高的趋势,但无显著差异;两组间的NE、DA和5-HT也无显著差异。合欢花组大鼠海马中的HVA、DA含量明显高于应激组,而前额叶中的多巴胺和5-羟色胺,以及纹状体中的5-羟色胺均明显低于应激组。这表明合欢花对慢性应激引起的大鼠生长受抑有缓解作用,对其脑内单胺类神经递质有调节作用。     

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.