A social environment influences the total RNA content of the brain cells of young laboratory rats

The paper describes the results of measurement of the total RNA content of single cells of the frontal pole of the cerebral cortex, the septum, the dorsal hippocampus and the medial hypothalamus of 35-day-old male laboratory (Wistar strain) rats. Two groups of ten animals each, reared in different ways, are compared: 1) young which lived from the age of 15 days with their mother, their siblings, other adult animals of both sexes and the young of other litters in a large, complex space, and 2) young which lived only with their mother and siblings in a small, simple space, as is usual under laboratory conditions. Nutrition and other environmental factors in the two groups were the same. The RNA content of cells from all the given parts of the brain was higher in community-reared rats, but the relative difference (related to the mean values for community-reared animals) in the various parts was not the same. It was smallest in the cerebral cortex and greatest in the dorsal hippocampus. Differences in the ventromedial hypothalamus and the septum were moderately large, with the hypothalamus rather resembling the cerebral cortex, while the septum differed statistically significantly from both the cortex and the hippocampus. The effect of social stimulation was thus strongest in the hippocampus.     

Cyclic adenosine-3',5'-monophosphate content in the limbic system structures of the rat brain on the administration of corticosteroids

The effect of hydrocortisone and DOCA on the cAMP content in the hypothalamus, hippocampus and striate body of the rat brain was investigated. Single (determined after 1 and 24 hours) and repeated (7 days) hydrocortison administration in a dose of 5 mg/100 g body weight was accompanied by an increase in the cAMP concentration in the brain structures under study. Single administration of DOCA in a dose of 0.5 mg/100 g body weight did not produce any changes in the cAMP level in the structures of the rat brain limbic system; however, the dose of 2.5 mg raised the cAMP level. Prolonged administration of the hormone in the above doses dod not change the cAMP level in the brain structures. Only the hippocampus showed a 210% increase in the cAMP level during DOCA administration in a dose of 0.5 mg.     

Determination of monoamines in rat brain regions after chronic administration of lithium

The effect of chronic administration of lithium on the concentration of biogenic amines and some of their metabolites in striatum, hippocampus, hypothalamus, pons-medulla and parietal cortex of rat were studied. Longterm lithium treatment modifies significantly the content of indoleamines in striatum and hypothalamus with minor changes in other structures. Catecholamine levels change after the treatment in striatum, hypothalamus, pons-medulla and parietal cortex. These results indicate that lithium treatment at therapeutic doses selectively modifies the catecholamine and indoleamine contents in discrete areas of the brain.     

Estrogens up-regulate type I and type II glucocorticoid receptors in brain regions from ovariectomized rats

The effects of 1-4 days of estradiol (E2) treatment on type I and type II glucocorticoid receptors (GCR) were determined in cytosolic fractions from brain regions of ovariectomized rats. Four days after E2 administration, type I GCR increased in septum, amygdala, hypothalamus and hippocampus, but decreased in the anterior pituitary. Type II GCR increased in septum and hypothalamus only. For both receptor types, changes occurred earlier in septum (1 day) than in the other regions. The E2 increment was due to an increase in Bmax, without changes in Kd. The up-regulation of type II GCR by E2 was also confirmed immunocytochemically in four nuclei of the septal area. In a parallel study, E2 receptors were determined in nuclear and cytosol fractions from the same regions analyzed for GCR. In rats receiving E2, estrogen receptors decreased in cytosol and increased in nuclei from septum, amygdala, hypothalamus and anterior pituitary, but did not change in hippocampus. The results suggest that GCR in certain neuroendocrine regions are regulated by E2, without taking into account whether the areas involved contain high (anterior pituitary), moderate (septum, hypothalamus, amygdala) or low (hippocampus) levels of E2 receptors. Our model may shed light on sex differences in GCR and on E2 regulation of glucocorticoid action in brain and the pituitary.     

Conditioned reflex analysis of functional connections between the hippocampus and limbic system structures

Instrumental defensive conditioned reflex elaborated in dogs to stimulation of the dorsal and ventral hippocampus, also appeared, due to generalization, in response to stimulation of a number of limbic structures. Two types of changes in the generalization effects (estimated by parameters of motor conditioned reaction) were observed in the course of conditioned reflex stabilization: enhancement (in response to stimulation of the lateral hypothalamus, lateral nucleus of septum, limbic cortex) and weakening toward complete disappearance (in response to stimulation of the medial nucleus of amygdala and medial hypothalamus). Manifestation of the generalization phenomenon from the brain structures, which are not involved initially into conditioned activity, suggests the existence of close functional connections between these structures and the hippocampus.     

Brain cell RNA: sexual differences in the rat.

Sexual differences in the total content of ribosomal RNA, established by cytophotometric measurements in neurones from selected brain regions, were studied in rats of the Wistar strain. In females of reproductive age, cyclic changes of RNA were synchronized with their oestrous cycle, the values being higher in the oestrous phase than in dioestrus. These changes were observed in pyramidal cells of the hippocampus and of the frontal cortex, in cells of anterior thalamus, of ventromedial and lateral hypothalamus and of tuberculi olfactorii. However, cycling cells were not disclosed in septum and thalamus posterior. A dependence upon the actual level of ovarial hormones was found in ventromedial hypothalamic cells only. In general, the RNA values in males of the same age corresponded to values of dioestrous females. The differences between newborn and 7-day-old pups were not marked enough and did not allow to define the critical period responsible for initiation of this sexual difference. In senescent rats, this difference persisted. During the stable phase of long-lasting dioestrus, the total RNA content in cells of the frontal cortex, hippocampus and hypothalamus was higher in females than in males of the same age which may suggest a faster reduction of this substance in aged males. The prolonged influence of oestrogens in the oestrous phase of the climacteric period (preceding the permanent dioestrus) decreased the RNA values in hippocampal and hypothalamic neurones even below the level established during the permanent dioestrus (and thus reached male values). On the contrary, in frontal cortical neurones, the female values remained higher in the permanent dioestrus as well as during long-lasting oestrus. A discussion concerns the possible participation of genetic determination and of the actual state of ovarial hormones in the manifestation of sexual differences in brain cells of the rat.     

Dose-dependent dual effect of corticosterone on cerebral 5-HT metabolism

The action of 1.0 and 10.0 mg/kg (i.p.) of corticosterone on serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) contents and on serotonin turnover, measured by an MAO-inhibitor method, was studied at 30 and 120 min after administration. A 1.0 mg/kg dose of corticosterone increased the serotonin content and turnover in the hypothalamus and mesencephalon 30 min after administration; however, it was ineffective on dorsal hippocampus and frontal and parietal cortex. 5-HIAA content did not change significantly in any of the brain areas studied. A 10.0 mg/kg dose of corticosterone decreased the serotonin content and turnover in the hypothalamus and mesencephalon; it was ineffective in other brain areas investigated. 5-HIAA content significantly decreased in the hypothalamus while it increased in the mesencephalon and dorsal hippocampus. In the parietal and frontal cortex, 5-HIAA content did not change following administration of 10.0 mg/kg of corticosterone. At 120 min after corticosterone administration, neither 5-HT content and turnover nor 5-HIAA content showed any change in the brain areas investigated. The results suggest that corticosteroids might change the activity of the brain serotoninergic system in a dose- and time-dependent manner, and in this way the serotoninergic system might play an important role in mediation of the corticosteroid effect exerted on brain function.     

Changes in dehydrogenase glutamate in the rat brain caused by thyroid hormone deficiency

The dependent GDH-NADPH activity in adenohypophysis and other cerebral areas, has been studied in hypothyroid rats, in which hypothyroidism has been induced surgically. After thyroidectomy a decrease of GDH activity in limbic system (amygdala, septum and hippocampus), and an increase of this enzyme in cortex and hypothalamus have been found, with no changes in adenohypophysis. The alterations of GDH activity, induced by thyroidectomy, have been corrected, although not uniformly in the different brain areas after L-T3 treatment.     

Beta-endorphin in brain limbic structures as neurochemical correlate of psychic dependence on drugs

The significance of beta-endorphin for drug dependence was explored by measuring the levels of beta-endorphin-immunoreactivity (beta E-IR) in plasma and parts of pituitary and brain of rats self-administering heroin or cocaine as compared to animals offered saline. Rats that had intravenously self-administrated heroin for 5 consecutive daily sessions of 6 h, and were decapitated immediately after the last session, showed a decreased concentration of beta E-IR in the anterior lobe (AL) of the pituitary while rats that had taken cocaine showed a decreased concentration of beta E-IR in the septum. Rats that had self-administrated heroin or cocaine and were decapitated 18 h after the last session, showed an increased concentration of beta E-IR in plasma and decreased concentrations in the AL of the pituitary and in specific areas of the brain limbic system, i.e. nucleus accumbens, septum, hippocampus and rostral striatum. The finding that self-administration of both the opiate heroin, inducing psychic and physical dependence, and the non-opiate cocaine, inducing psychic but not physical dependence, is accompanied by similar changes in beta E-IR concentrations particularly in limbic brain structures, and that these effects are present 18 h but not immediately after the last session, suggests that beta E and related peptides in limbic brain regions may represent a neurochemical correlate for psychic dependence on drugs.     

Neurochemical effects of the endocannabinoid uptake inhibitor UCM707 in various rat brain regions

To date, UCM707, (5Z,8Z,11Z,14Z)-N-(3-furylmethyl)eicosa-5,8,11,14-tetraenamide, has the highest potency and selectivity in vitro and in vivo as inhibitor of the endocannabinoid uptake. Its biochemical, pharmacological and therapeutic properties have been intensely studied recently, but the information on its capability to modify neurotransmitter activity, which obviously underlies the above properties, is still limited. In the present study, we conducted a time-course experiment in rats aimed at examining the neurochemical effects of UCM707 in several brain regions following a subchronic administration (5 injections during 2.5 days) of this inhibitor in a dose of 5 mg/kg weight. In the hypothalamus, the administration of UCM707 did not modify GABA contents but reduced norepinephrine levels at 5 h after administration, followed by an increase at 12 h. Similar trends were observed for dopamine, whereas serotonin content remained elevated at 1 and, in particular, 5 and 12 h after administration. In the case of the basal ganglia, UCM707 reduced GABA content in the substantia nigra but only at longer (5 or 12 h) times after administration. There were no changes in serotonin content, but a marked reduction in its metabolite 5HIAA was recorded in the substantia nigra. The same pattern was found for dopamine, contents of which were not altered by UCM707 in the caudate-putamen, but its major metabolite DOPAC exhibited a marked decrease at 5 h. In the cerebellum, UCM707 reduced GABA, serotonin and norepinephrine content, but only the reduction found for norepinephrine at 5 h reached statistical significance. The administration of UCM707 did not modify the contents of these neurotransmitters in the hippocampus and the frontal cortex. Lastly, in the case of limbic structures, the administration of UCM707 markedly reduced dopamine content in the nucleus accumbens at 5 h, whereas GABA content remained unchanged in this structure and also in the ventral-tegmental area and the amygdala. By contrast, norepinephrine and serotonin content increased at 5 h in the nucleus accumbens, but not in the other two limbic structures. In summary, UCM707 administered subchronically modified the contents of serotonin, GABA, dopamine and/or norepinephrine with a pattern strongly different in each brain region. So, changes in GABA transmission (decrease) were restricted to the substantia nigra, but did not appear in other regions, whereas dopamine transmission was also altered in the caudate-putamen and the nucleus accumbens. By contrast, norepinephrine and serotonin were altered by UCM707 in the hypothalamus, cerebellum (only norepinephrine), and nucleus accumbens, exhibiting biphasic effects in some cases.     

Synaptic changes in cortical and subcortical brain formations in old rats

Electron microscopy was used to study structural changes of synapses in sensorimotor, parietal, limbic cortical areas, hippocamp, blue spot and hypothalamus of old Wistar rats, aged 28-30 months. Polymorphism of ultrastructural changes in neuronal and synapse processes and individual variability of these shifts in the brain of old rats have been revealed. The predominant damage of post-synaptic synapse components with ageing is demonstrated. Along with dystrophic and destructive changes in pre- and post-synaptic parts of the contact, signs of compensatory adaptive resettings in inter-neuronal links have been detected.     

Brain monoamines following castration of aggressive muricidal rats

The effect of castration on the levels of brain monoamines and their metabolites has been investigated in rats which became or did not become muricidal following long-term isolation. Fourteen brain areas were explored: olfactory bulbs (OB), olfactory tubercles (OT), septum (Se), striatum (Sr), amygdala (A), thalamus (Th), hypothalamus (Hy), hippocampus (Hi), superior colliculus (SC), inferior colliculus (IC), raphe (Ra), pons-medulla (PM), frontal cortex (FC), temporal cortex (TC) and parietal cortex (PC). Except in the raphe of non muricidal rats and in the striatum of muricidal animals, all other areas examined demonstrate some changes of monoamines neurotransmitter or their metabolites after castration. The strongest changes, always increases, were found in the thalamus. In several brain areas, the changes occurring after castration, differ quantitatively and qualitatively in muricidal and non-muricidal rats.Special issue dedicated to Dr. Claude Baxter.Prof. P. Mandel passed away on October 6th, 1992.     

Changes in the rate of local cerebral blood flow and cytochrome concentration in several areas of the brain of the albino rat during neurotization

In several brain parts of rats with experimental neurosis local circulation rate (LCR) was measured by hydrogen clearence method, and cytochromes content was determined by differential spectrophotometry. In early period of neurotization (up to 15 days) reciprocal LCR changes were observed in the cortex and subcortical structures, and after 18 days were reduced in all the brain parts studied. The maximum reduction was observed after three weeks of neurotization. Neurotization during one week elicited significant decrease of cytochrome a level in the cortex. Its level in the cortex after 3 weeks of neurotization and in the hypothalamus and hippocampus after one and three weeks of neurotization did not differ from its normal content. Neurotization did not influence cytochromes c + c1 levels in the structures examined.     

Effect of swinging on EEG of rats of juvenile age in the wakefulness state

Simultaneous recording of the EEG activity of superficial cortical and deep (caudate nucleus, dorsal hippocampus, anterior hypothalamus) brain parts has been performed for the first time after a 2-h swinging of frequency of 0.2 Hz in Wistar rats of juvenile age. Swinging was produced on a 4-bar parallel swing. Using a Neuron-Spectr electroencephalograph and a Diana program, normalized power spectra of wave EEG components, synchronization coefficients, and coefficients of cross-correlation between bioelectrical potentials of various brain structures were determined. After a 2-h swinging, the mean value of normalized power of slow waves of delta-diapason in hypothalamus and hippocampus was found to increase statistically significantly, while normalized power of fast waves of alpha- and beta1-diapasons in hippocampus decreased (p < 0.05). A statistically significant increase of synchronization coefficient was observed in hypothalamus and hippocampus. Changes of coefficients of cross-correlation between hypothalamus and hippocampus and other brain strictures were of the oppositely directed, individual character. In the parietal occipital brain cortex and in caudate nucleus, the changes of the EEG spectral composition also were of individual character. The obtained results on the whole correspond to data about an enhancement of the EEG low-frequency rhythms at swinging and agree with the resonance hypothesis of motion sickness.     

GABA-ergic system in brain regions of glutamate-lesioned rats

Subcutaneous administration of high doses of glutamate to rats during their first 10 days after birth produced a great reduction of GABA content and GAD activity in the adult mediobasal hypothalamus, both in male and female. In addition GABA content and GAD activity showed a slight significant decrease in female cerebellum and male striatum. Glutamate treatment was also followed by a significant increase in GABA content and GAD activity of male substantia nigra, cerebellum, hippocampus and of female olfactory bulb. No reduction in GABA-T activity was observed in different brain areas studied except in mediobasal hypothalamus. The results support the view that glutamate treatment had a direct toxic effect on GABA-ergic neurons in mediobasal hypothalamus. The changes in GAD activity observed in all areas studied may reflect the neuroendocrine changes determined by nucleus arcuate lesions.     

Behavioural, biochemical and histological effects of trimethyltin (TMT) induced brain damage in the rat.

To assess the nature and extent of behavioural, biochemical and histological changes induced by trimethyltin (TMT), rats were treated with a single injection of TMT over a dose range of 6, 7 and 8 mg/kg i.p. Behavioural observations were performed at a minimum of 21 days after the administration of TMT. The behavioural consequences of TMT were hyperactivity in the open-field test, increased locomotor activity and deficits in passive and active avoidance behaviour, T-maze alternation and Morris Water Maze behaviour. The behavioural changes were dose dependent and were accompanied by a degree of pathological damage to the hippocampal pyramidal cells which was particularly apparent at the highest dose. The main biochemical effects of TMT involved deficits in the serotonergic and GABA-ergic systems and a decrease in M1 and M2 binding sites in the hippocampus. These results suggest that the toxic interaction of TMT with the hippocampus and other limbic brain regions may be responsible for its effect on learning and memory.     

抗体应答期间大鼠脑和胸腺中儿茶酚胺含量的变化

目的：探讨在抗体应答期间,脑和淋巴器官中儿茶酚胺（ＣＡｓ）含量的动态变化,籍以了解免疫状态对中枢和外周ＣＡｓ神经活动的影响。方法：用绵羊红细胞（ＳＲＢＣ）免疫大鼠,在免疫后第２￣７ｄ应用高效液相色谱－电化学检测法（ＨＰＬＣ－ＥＣＤ）测定大鼠下丘脑、海马、脑干和胸腺中云甲肾上腺素（ＮＡ）、肾上腺素（Ａ）、多巴胺（ＤＡ）和高香草酸（ＨＶＡ）的含量。结果：①下且脑和海马内ＮＡ在抗体应答期间升高,而胸腺中     

Chronic ingestion of ethanol or glucose solutions affects hypothalamic and limbic TRH metabolism in dams and their pups

The effect of chronic ethanol consumption during pregnancy and lactation on thyrotropin releasing hormone (TRH) metabolism was investigated in the hypothalamus and limbic areas of female rats and their weaned pups. Pregnant female rats received ethanol or isocaloric glucose solution during pregnancy either alone, or also during the 3 weeks of lactation. Thyrotropin (TSH) and corticosterone levels were measured in serum; TRH and TRH-gly concentrations were determined in hypothalamus, hippocampus, n.accumbens, frontal cortex and amygdala of dams and pups at 21 days after parturition. Ethanol or glucose consumption during pregnancy and lactation produced a decrease in TSH levels compared with control animals fed at libitum; water replacement during lactation normalized TSH levels only in glucose-fed dams. Pups from ethanol or pair-fed dams showed low weight and increased TSH levels compared with normal rats. Variations in TRH metabolism were detected in limbic areas. Chronic ethanol caused a decrease in the levels of TRH in the hippocampus and frontal cortex of dams. In contrast, glucose chronic ingestion increased TRH content specifically in n.accumbens and amygdala of dams. Most of the variations in TRH content of limbic areas of pups were not specific for glucose or ethanol treatment and correlated with the deleterious effect of the mother's thyroid condition, although some differences were observed depending on pup's gender. These results support the involvement of TRHergic neurons in the limbic system of the female rat exposed to alcohol or glucose during pregnancy and lactation.     

Influence of short-lasting bilateral clamping of carotid arteries (BCCA) on GABA turnover in rat brain structures

We have previously shown that short-lasting reduction of cerebral blood flow by bilateral clamping of carotid arteries (BCCA) results in long-lasting increase in regional GABA concentration and decrease in seizure susceptibility in rats. In the present experiments, the effect of BCCA on GABA turnover and the enzymes involved in GABA synthesis and degradation were studied in rats. Regional GABA turnover was measured by means of GABA accumulation induced by the GABA-transaminase (GABA-T) inhibitor aminooxyacetic acid (AOAA). Fourteen days after BCCA, GABA turnover was significantly increased in hippocampus, substantia nigra and cortex, but not different from sham-operated controls in several other brain regions, including striatum, hypothalamus and cerebellum. The activity of glutamate decarboxylase (GAD) measured ex vivo did not show any changes in investigated structures, while the activity of GABA-T was slightly increased in hippocampus. The increased GABA turnover in some brain regions may explain our previous findings of increased GABA content in these brain regions and decreased sensitivity of BCCA treated animals to the GABA_A-receptor antagonist bicuculline.     

Effect of swinging on EEG of rats of juvenile age in the wakefulness state

Simultaneous recording of the EEG activity of superficial cortical and deep (caudate nucleus, dorsal hippocampus, anterior hypothalamus) brain parts has been performed for the first time after a 2-h swinging of frequency of 0.2 Hz in Wistar rats of juvenile age. Swinging was produced on a 4-bar parallel swing. Using a Neuron-Spectre electroencephalograph and a Diana program, normalized power spectra of wave EEG components, synchronization coefficients, and coefficients of cross-correlation between bioelectrical potentials of various brain structures were determined. After a 2-h swinging, the mean value of normalized power of slow waves of δ-diapason in hypothalamus and hippocampus was found to increase statistically significantly, while normalized power of fast waves of α-and β₁-diapasons in hippocampus decreased (p < 0.05). A statistically significant increase of synchronization coefficient was observed in hypothalamus and hippocampus. Changes of coefficients of cross-correlation between hypothalamus and hippocampus and other brain strictures were of the oppositely directed, individual character. In the parietal occipital brain cortex and in caudate nucleus, the changes of the EEG spectral composition also were of individual character. The obtained results on the whole correspond to data about an enhancement of the EEG low-frequency rhythms at swinging and agree with the resonance hypothesis of motion sickness.