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Biomedical subjects

B Bohus

Publications and source records attributed to B Bohus.

At least 55 records · Page 3Linked to original sources
PubMed1995

Behavioural activation produced by CRH but not alpha-helical CRH (CRH-receptor antagonist) when microinfused into the central nucleus of the amygdala under stress-free conditions.

The central nucleus of the amygdala (CeA) is known to be involved in the regulation of autonomic, neuroendocrine, and behavioural responses in stress situations. The CeA contains large numbers of corticotropin-releasing hormone (CRH)-containing cell bodies and terminals. In the present study we examined (by continuous behaviour observations) the effects of a high dose of CRH (150 ng) and two doses of the CRH-receptor antagonist (alpha-hCRH: 1.0 and 0.1 micrograms) after microinfusion into the CeA in freely moving male Wistar rats under stress-free conditions. In comparison with control, alpha-hCRH infusion did not cause any behavioural activation. In contrast CRH-infusion revealed a long-lasting increase in grooming and exploration with a concomitant decrease in behaviours specified as resting. These results indicate that the CRH system in the CeA does not seem to be activated in stress-free conditions, but its activation is of importance for active behavioural responses.

Amygdala↗
PubMed1995

Cardiovascular effects and changes in midbrain periaqueductal gray neuronal activity induced by electrical stimulation of the hypothalamus in the rat.

The effects of low-intensity electrical stimulation of sites in the hypothalamus and zona incerta (ZI) on mean blood pressure (MBP), heart rate (HR), and neuronal activity in the midbrain periaqueductal gray (PAG) were investigated in rats. Long-lasting depressor responses were elicited from 67 sites in the hypothalamus and ZI. Effects on HR were variable, except for the ZI where bradycardiac responses were evoked. The amplitude of the depressor responses was significantly correlated with baseline MBP on stimulation of the dorsomedial hypothalamic nucleus (DMH) or the dorsal hypothalamic area. Extracellular single-unit recordings were made from 94 PAG neurons. Most units were located in the ventral half of the PAG (62/94), where spontaneous firing rates were significantly higher than in the dorsal half: 12.5 +/- 1.4 spikes/s as compared to 6.0 +/- 0.9 spikes/s. Changes in PAG neuronal activity to both ipsi- and contralateral hypothalamic stimulation were observed. Most neurons were inhibited or unresponsive. There was no site specificity: responsive and unresponsive neurons were scattered throughout the PAG. Inhibition was most effectively evoked by stimulation of the DMH (25 out of 39 neurons) and the ZI (9 out of 15 neurons). In most neurons, the inhibition strictly followed the time course of hypothalamic stimulation. The results suggest that PAG as well as nonPAG pathways participate in the hypothalamic control of cardiovascular function.

Animals↗
PubMed1995

Electrophysiological analysis of midbrain periaqueductal gray influence on cardiovascular neurons in the ventrolateral medulla oblongata.

Stimulation of sites in the rostral or caudoventral periaqueductal gray (PAG) results in substantial increases in mean blood pressure (MBP) and heart rate (HR). The efferent pathways from these PAG subregions possibly include a relay in the ventrolateral medulla oblongata (VLM), where neurons involved in maintaining vasomotor tone are located. Extracellular recordings were made from 21 cardiovascular neurons in the rostral VLM (RVLM) and from 6 cardiovascular neurons in the caudal VLM (CVLM) of the rat. These neurons showed barosensitivity and cardiac rhythmicity. In addition, the activity of 54 non- cardiovascular and nonrespiratory units was recorded. Responses to electrical stimulation of sites in the (rostral or caudal) PAG were studied in 16 of the 21 cardiovascular RVLM neurons, the 6 CVLM neurons, and 46 of the 54 noncardiovascular neurons. Eight of the RVLM neurons were excited by rostral PAG stimulation; the poststimulus time histograms showed a constant latency in live units (32 +/- 3 ms). This suggests the presence of relatively direct (although not monosynaptic) excitatory pathways from the rostral PAG to cardiovascular neurons in the RVLM, consisting of slowly conducting fibers (0.2-0.3 m/s). Five RVLM neurons did not respond to rostral PAG stimulation. Three units were tested with caudal PAG stimulation: one was excited, one inhibited, and one was unresponsive. The six cardiovascular CVLM neurons did not respond to PAG stimulation. Of the 46 noncardiovascular neurons, 14 cells were excited, 7 inhibited, and 2 cells antidromically activated. These results confirm earlier findings, extending them to the rostral PAG. They supply further evidence for the influence of the PAG on the cardiovascular function-related neuronal circuitry in the VLM.

Animals↗
PubMed1995

Synthesis and organ distribution of [18F]fluoro-Org 6141 in the rat: a potential glucocorticoid receptor ligand for positron emission tomography.

For the synthesis of [18F]Fluoro-Org 6141 via a nucleophilic substitution reaction with 18F-, the tosyl group was chosen as the leaving group because of its stability and excellent leaving group ability. The biodistribution of the high affinity and moderate lipophilicity (log P = 2.66, calculated value) ligand [18F]Fluoro-Org 6141 (specific activity 8.2 to 37 TBq/mmol, yield 10% at EOB) was examined in sham adrenalectomized (sADX) and adrenalectomized (ADX) male Wistar rats. Two days after ADX or sADX, the animals were anesthetized and 0.37 to 1.85 MBq of [18F]Fluoro-Org 6141 was administered intravenously. Kinetics of 18F activity uptake were monitored for 3 h using a stationary double-headed positron emission tomography (PET) camera, and the biodistribution was assessed by ex vivo determination of radioactivity in several tissues and different brain areas. One hour after injection of the radioligand, the bladder, kidney, liver, trachea, and bone of sADX animals contained more concentration on a wet weight basis than blood. Three hours post injection, radioactivity was retained in bladder, trachea, and bone. The accumulation of radioactivity in brain corresponded to the concentration of activity in the blood within the first hours after injection. ADX animals showed a higher uptake of 18F activity in spleen, testes, and brain areas (hippocampus and brainstem) but a lower uptake in bone than sADX rats. PET scans suggested that 18F activity uptake in the brain had not yet reached a maximum at this interval. Although [18F]Fluoro-Org 6141 is not useful for PET studies of glucocorticoid receptors (GRs), the results obtained with this compound indicate a synthetic strategy suitable for the synthesis of high-affinity radioligands for GRs.

Animals↗
PubMed1995

The first derivation of the Frank Lead ECG at alterations of pulmonary ventilation in young healthy women.

The Frank orthogonal corrected ECG and its first derivation were recorded in 27 healthy volunteers (women aged 19-22 years) during normal ventilation at rest (control group), after voluntary hyperventilation lasting 75 seconds, and during hypoxic-hypercapnic ventilation (through the enlarged dead space) lasting 5 min. The projections of the magnitude and direction of the positive and negative QRS derivation maxima into the horizontal, frontal, left sagittal planes and their spatial distribution were constructed. The magnitude of the positive and negative QRS derivation maxima was significantly decreased during hypoxic-hypercapnic ventilation. A significant alteration in the direction only arose at the positive maximum during hypoxic-hypercapnic ventilation in the frontal plane. The intrinsicoid deflection was not significantly altered. The normal values of the maxima of the first QRS derivation in young healthy women are given. It is supposed that the decrease in amplitude of the maxima of the first QRS derivation is caused by slowed propagation of the depolarization wave under hypoxic-hypercapnic conditions and alteration of the direction of the positive maximum is caused by a greater participation of the right ventricle at the origin of the resulting QRS vector.

Adult↗
PubMed1994

Effect of corticotropin-releasing factor antagonist on behavioral and neuroendocrine responses during exposure to defensive burying paradigm in rats.

Defensive burying behavior is a coping strategy in rodents in response to an aversive stimulus where fear will facilitate burying and treatment with anxiolytics will result in less burying. To test the hypothesis that endogenous corticotropin-releasing factor (CRF) is involved in the defensive burying response, the effects of an ICV CRF antagonist were tested on defensive burying behaviors as well as the plasma adrenocorticotropic hormone (ACTH) and plasma corticosterone response. Rats were allowed to self-administer one mild electric shock (1.0 mA) through a probe mounted on the wall of the home cage by briefly touching it. Following this shock, control rats typically display burying behavior, as defined as moving the bedding material toward and/or over the shock probe. A CRF antagonist, alpha-hel CRF9-41, was administered ICV (1, 5, and 25 micrograms) 1 min after they received the shock. The 5 micrograms dose of the CRF antagonist significantly attenuated the time spent in defensive burying compared to vehicle-treated controls. The 5 and 25 micrograms doses of alpha-hel CRF9-41 increased the latency to display defensive burying. However, the enhanced release of plasma ACTH and plasma corticosterone concentrations in the stressed animals was not significantly modified over the 15-min period by either of the three doses of CRF antagonist. The results suggest that endogenous CRF is involved in the expression of defensive burying behavior and that the brain CRF receptors modulating the behavioral response may be different from the CRF receptors modulating the hormonal response of defensive burying.

Adrenocorticotropic Hormone↗
PubMed1993

Corticotropin-releasing hormone microinfusion in the central amygdala diminishes a cardiac parasympathetic outflow under stress-free conditions.

The central nucleus of the amygdala (CeA) is known to be involved in the regulation of autonomic, neuroendocrine and behavioural responses in stress situations. The CeA contains large numbers of corticotropin-releasing hormone (CRH) cell bodies. Neuroanatomical studies revealed that the majority of the CRH fibres from the CeA have direct connections with autonomic regulatory nuclei in the brainstem. In the present study, the effects of locally infused CRH (30 ng) into the CeA, in freely moving male Wistar rats under stress-free conditions, were examined. Heart rate, endocrine parameters and behavioural activity were repeatedly measured before, during and after local administration of CRH, pretreated with either artificial CSF or the CRH-receptor antagonist, alpha-helical CRH (alpha-hCRH). CRH infusion alone caused a long-lasting increase in heart rate without affecting plasma adrenaline and noradrenaline as indicators of sympathetic activity. This CRH-induced tachycardia was effectively blocked by pretreatment with a high dose (1 microgram) alpha-hCRH locally into the CeA, while the pretreatment with low dose (0.1 microgram) of the alpha-hCRH caused a minor blockade of the CRH-induced tachycardia. The results suggest that CRH mechanisms in the CeA regulate the autonomic changes probably only by affecting parasympathetic but not sympathetic output systems. Because CRH is given at the level of the cell body of the CRH neurons in the CeA, we suggest that the reduction of the parasympathetic output may be explained as an autoreceptor-mediated inhibition of CRH neurons from the CeA with parasympathetic-regulating brainstem nuclei.

Amygdala↗
PubMed1993

Propagation of epileptiform activity during development of amygdala kindling in rats: linear and non-linear association between ipsi- and contralateral sites.

The relationship between ipsi- and contralateral epileptiform electroencephalographic (EEG) activity was investigated in rats that were kindled daily in the amygdala. Two types of relationships--linear and non-linear associations--were studied and used to estimate time delays of EEG activity between homotopic amygdalar sites during consecutive tetanizations. The progressive development of epileptiform EEG and convulsive behaviour was accompanied by an increase in association. Maximal association values of the non-linear function were significantly higher than linear association values. The gradual development of motor seizure severity was correlated with increased non-linearity. Time delays between the two amygdalae were estimated comparably with the linear and non-linear function: 30.0 +/- 3.3 and 24.6 +/- 1.7 ms (ipsilateral leading contralateral), respectively. However, in rats displaying exclusively bilaterally generalized motor convulsions, maximal values of both functions decreased but were still significantly higher than control values of phase-randomized EEG. Corresponding positive as well as negative interhemispheric time delays were recorded during the afterdischarge. These results demonstrated a strengthened association between the ipsi- and contralateral amygdala during primary epileptogenesis induced by amygdala kindling. In contrast, development of a secondary focus in the contralateral homotopic region resulted in a weakened interhemispheric association. Secondary bilateral synchrony between the ipsi- and contralateral amygdala occurred during the evoked epileptiform EEG activity.

Animals↗
PubMed1993

A single social stress-experience alters glutamate receptor-binding in rat hippocampal CA3 area.

The distribution of glutamate receptors in the rat hippocampus was investigated 24 h after the social stress of confrontation with a dominant opponent. AMPA-type glutamate receptors were labeled with the antagonist [3H]CNQX, and NMDA-type receptors were labeled with the competitive antagonist [3H]CGP39653. Increased [3H]CGP39653 labeling was exclusively found in the CA3 stratum radiatum and a decreased [3H]CNQX labeling was found in several hippocampal areas. Consequently, the ratio NMDA/AMPA binding was significantly increased in CA3 stratum oriens and CA3 stratum radiatum. These results suggest that a single unescapable social stress of defeat alters the impact of the excitatory neurotransmitter glutamate, which is restricted to hippocampal CA3 neurons. Possible consequences of the present findings are discussed.

2-Amino-5-phosphonovalerate↗
PubMed1993

Central actions of corticotropin-releasing hormone (CRH) on behavioral, neuroendocrine, and cardiovascular regulation: brain corticoid receptor involvement.

The effect of intracerebroventricular (icv) infused corticotropin-releasing hormone (CRH), 300 ng, infused at a rate of 16.67 ng/min during 18 min and its relation to the functioning of brain corticoid receptors was investigated in freely moving rats in their home cages. Behavior was sampled before, during, and after the CRH infusion. Cardiovascular measurements were made via a chronically implanted catheter in the descending aorta. Blood samples were withdrawn to determine adrenal hormone concentration. Central administration of the brain mineralocorticoid-like receptor (MR) antagonist (RU 28318, 100 ng) and the glucocorticoid receptor (GR) antagonist (RU 38486, 100 ng) 60 min before CRH infusion served to manipulate adrenal steroid states in the brain. CRH infusion caused behavioral activation which was associated with an increase in heart rate (HR) and mean arterial blood pressure (MAP). Increased plasma corticosterone and norepinephrine levels were observed, while a minor elevation of epinephrine (E) levels also occurred. Both corticoid receptor antagonists failed to affect the CRH-induced behavioral activation. Administration of the GR antagonist significantly enhanced the magnitude of the CRH-induced increase in E, whereas the effect of the MR antagonist just failed to reach significance. These findings suggest the involvement of central corticoid receptors in sympathoadrenomedullary feedback mechanisms. The MR antagonist elevated baseline MAP probably thereby suppressing the magnitude of the CRH response. The increase in HR was diminished by both antagonists shortly after CRH infusion. Together, the data suggest involvement of brain corticosteroid receptor-mediated processes in neuroendocrine and cardiovascular effects of CRH.

Animals↗
PubMed1993

Differential perinatal testosterone secretory capacity of wild house mice testes is related to aggressiveness in adulthood.

Testosterone secretory capacity of testicular Leydig cells was determined in fetal males of an aggressive and a nonaggressive genetic selection line of wild house mice. They were studied at Days 15-18 of gestation and on the first day after birth. A previously described morphometric method was used to quantify 3 beta-hydroxy steroid dehydrogenase (3 beta-HSD)-stained Leydig cells in testicular sections to determine testosterone secretory capacity, which may be considered to reflect circulating plasma testosterone in the fetus. The results of this study show that the testosterone secretory capacity of Leydig cells in the testis changes differentially during intrauterine development in males of the aggressive and nonaggressive selection lines. The peak secretory capacity is reached at Day 17 of gestation for the males of the aggressive selection line, while the peak for the nonaggressive males is reached on the first neonatal day. The larger anogenital distance observed in aggressive males suggests a higher prenatal testosterone level in these males. The importance of the difference in timing of the perinatal 3 beta-HSD peak top individual variation in adult aggressive behavior is discussed.

3-Hydroxysteroid Dehydrogenases↗
PubMed1993

Genetic differences in female house mice in aggressive response to sex steroid hormone treatment.

Male mice, genetically selected for aggression, characterized by short attack latency (SAL) or long attack latency (LAL), differ on several testosterone (T)-related parameters during ontogeny and adult age. The variation in aggressive behavior at adult age may be due to differences in degree of androgenization prenatally. When exposed to T at prenatal, neonatal, and/or adult age, nonlactating females also display intraspecific fighting behavior. In the present study, we investigated in females of the SAL and LAL selection lines, whether the differentiation of aggression involves processes similar to ones seen in males. Therefore, we injected females with testosterone propionate (TP) or vehicle on the day of birth, treated them after ovariectomy at adult age with T, estradiol (E), or vehicle, and tested their aggressive response. We found that neonatally vehicle-treated SAL females show a higher aggressive response to chronic T treatment at adult age than LAL females receiving the same treatment. Females of both selection lines treated with vehicle or E as adults were not aggressive. Neonatal TP treatment did not influence the adult T sensitivity and difference between selection lines in response to T at adult age. However, neonatally TP-treated SAL females showed aggressive behavior when treated with E at adult age, whereas LAL females failed to do so. These results suggest a genetic difference in susceptibility to T and E, which plays a major role prenatally, in organizing the development of sex steroid-dependent neural systems.

Aggression↗
PubMed1993

Neuroendocrine and behavioral effects of vasopressin in resting and mild stress conditions.

Neuroendocrine and behavioral effects of subcutaneously administered AVP (6 micrograms/kg b.wt.) were determined in resting conditions and after the mild stress of transportation to and placement in a novel environment. In resting conditions, systemic administration of AVP caused a rapid increase in blood glucose level and a long-lasting increase in CORT secretion. A decrease in circulating plasma NE level was observed. AVP did not affect adrenal medullary E secretion. The stress-induced sympathetic activation, as reflected in plasma NE level, was inhibited 60 min after AVP administration. Stress-induced increases in blood glucose, CORT, and E secretion were not influenced by AVP. In resting condition, AVP caused a 60-min lasting increase in grooming behavior with a concomitant decrease in time spent resting. Sixty minutes after administration, the behavioral activation after the stress of transportation and placement in a novel environment was more rapidly terminated in AVP-treated rats than in vehicle-treated control rats. The state- and time-dependent modulation of spontaneous behavior suggests that AVP has arousing properties shortly after administration when marked pressor and endocrine effects are apparent. In a later phase, AVP may facilitate dearousal mechanisms following stress-induced behavioral activation.

Animals↗
PubMed1993

The central amygdala is involved in conditioning but not in retention of active and passive shock avoidance in male rats.

The present study was designed to further characterize the involvement of the central amygdaloid nucleus (CEA) in the conditioning and the retention of both active and passive stress-related behaviors. Active shock avoidance was investigated in a shuttle-box. CEA-lesioned and sham-operated animals received 30 trials on 2 consecutive days. During the first day of conditioning, the CEA-lesioned animals failed to learn to avoid, but on the second day these rats showed avoidance behavior that was comparable to the sham-lesioned ones. When lesioned animals received a total of 60 trials on 1 day, they failed to show avoidance, suggesting deficits in acquisition performance but presence of latent learning following CEA lesioning. However, the retention response, which was studied by lesioning the CEA between a 2-day avoidance training and a retention test, was unaffected. Stress-related learning was also studied in a test of passive avoidance of a previously received single, inescapable electric footshock. When the lesion was placed before the single learning trial, the retention of the response was absent. However, CEA-lesioning after the learning trial revealed no differences between the CEA-lesioned and sham-lesioned animals. In conclusion, these results demonstrate that the CEA is involved in the conditioning rather than retention of both active and passive shock avoidance responses.

Amygdala↗
PubMed1993

Colocalization of muscarinic acetylcholine receptors and protein kinase C gamma in rat parietal cortex.

The present investigation analyzes the cellular distribution of muscarinic acetylcholine receptors (mAChRs) and the gamma isoform of protein kinase C (PKC) in the rat parietal cortex employing the monoclonal antibodies M35 and 36G9, respectively. Muscarinic cholinoceptive neurons were most present in layers 2, 3 and 5, whereas most PKC gamma-positive cells were found in layers 2, 5 and 6. Under normal, non-stimulated conditions, approximately 58% of all muscarinic cholinoceptive neurons were immunoreactive for PKC gamma. Conversely, nearly all PKC gamma-positive neurons were M35-immunoreactive. Although both pyramidal and nonpyramidal neurons express the two types of protein, the pyramidal cell type represents the vast majority. Of all cortical neurons, the large (15-25 microns in diameter) muscarinic cholinoceptive pyramidal neurons in layer 5 express the gamma isoform of PKC most abundantly and most frequently. Approximately 96% of these cells are immunoreactive for PKC gamma. Stimulation of mAChRs by the cholinergic agonist carbachol resulted in a pronounced increase in the intensity of 36G9 immunoreactivity, which may suggest that the mAChRs are functionally linked to the colocalized PKC gamma. No change was found in the number of 36G9-immunoreactive neurons. In contrast, the number of immunocytochemically detectable muscarinic cholinoceptive neurons increased by approximately 38% after carbachol stimulation. The high degree of codistribution in cortical neurons of both transduction proteins suggests a considerable cholinergic impact upon the regulation of PKC gamma, a candidate key enzyme in cortical learning and memory mechanisms.

Animals↗
PubMed1993

Long-term increase in protein kinase C-gamma and muscarinic acetylcholine receptor expression in the cerebral cortex of amygdala-kindled rats--a quantitative immunocytochemical study.

Kindling is an animal model for epilepsy in which repeated application of an electrical stimulus to brain pathways results in an epileptic focus. The animal holds a permanent state of hyperexcitability to the stimulus for the rest of its life. Understanding the cellular and molecular processes underlying hyperexcitability could provide insight into epileptogenesis. Furthermore, it could elucidate cellular and molecular bases of synaptic plasticity in the central nervous system. In the present study the long-term effect of a kindled focus in the amygdala on the gamma-isoform of protein kinase C and the muscarinic cholinergic receptor as cellular messengers was evaluated in the cerebral cortex of rats. Following an average of 10 bilaterally generalized seizures kindling stimulation was terminated and rats were left undisturbed for approximately three months. Brains were processed by immunocytochemistry using monoclonal antibodies against protein kinase C-gamma and muscarinic cholinergic receptor protein. Digital image analysis of sections through the entire forebrain revealed an increase in optical density of both protein kinase C-gamma and the muscarinic cholinergic receptor in the piriform and entorhinal cortex of the hemisphere contralateral to the stimulation site in kindled rats. However, on the ipsilateral side no change was observed in comparison with electrode implanted nonkindled control rats. The observed increase in expression of muscarinic cholinergic receptor protein and a component of the phosphoinositide second messenger system (protein kinase C-gamma) located in specific areas of the cerebral cortex in kindled rats could serve as a basis for the permanent state of hyperexcitability in these rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Amygdala↗