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Biomedical subjects

B Bohus

Publications and source records attributed to B Bohus.

At least 109 records · Page 6Linked to original sources

Hippocampal kindling-induced after-discharge and behavioural depression: immediate and long-term attenuation by opiate antagonists.

Hippocampal kindling results in tonic-clonic convulsions followed by a pronounced period of behavioural depression. The effect of the opiate antagonists, naltrexone and naloxone, on the duration of the after-discharge and behavioural depression was investigated. Naltrexone, injected s.c. 60 min before, significantly reduced the behavioural depression at doses as low as 0.6 mg/kg, but had no effect on the after-discharge even at higher doses. One day later, the behavioural depression was still reduced in some animals and the after-discharge was significantly decreased following the higher doses (0.24-0.48 mg/kg). Naloxone, injected s.c., 10 min before, significantly reduced the behavioural depression at a dose as low as 0.002 mg/kg and also reduced the duration of the after-discharge at some doses. Naloxone did not exert any significant effects 24 h later. Naltrexone, injected i.c. 60 min before kindling in a dose of 1 microgram, significantly attenuated the behavioural depression and had no effect on the after-discharge. The behavioural depression was still attenuated 24 and 48 h later. The involvement of mu-receptor-related endogenous opioid mechanisms in postictal brain processes is suggested. The long-term effects might be related to receptor 'activation' during the immediate period due to an interaction between the antagonist and the kindling experience.

Animals↗

The propensity for schedule-induced polydipsia is related to differences in conditioned avoidance behaviour and in defense reactions in a defeat test.

In line with previous research showing that animals predisposed to develop schedule-induced polydipsia when submitted to intermittent distribution of food show differential behavioural and neurochemical characteristics, the present experiments investigated the nature of defense reactions to aversive situations in rats that do or do not develop schedule-induced polydipsia. It was found that rats that engage in excessive drinking during intermittent feeding display more rapid active avoidance learning in a 2-way shuttle-box and show less freezing when confronted with an aggressive resident male in a defeat test than those that do not develop schedule-induced polydipsia. These results are consistent with the hypothesis that individual differences in the propensity to exhibit oral consummatory activities in conditions of mild stress are related to the ability to shift behavioural programmes in response to external stimulation.

Aggression↗

Hypothalamic food intake regulating areas are involved in the homeostasis of blood glucose and plasma FFA levels.

The hypothalamus fulfills multiple functions, e.g., integration of food and water ingestion, various forms of social behavior and physiological neuroendocrine activities. Hypothalamic areas, particularly the ventromedial, lateral and paraventricular areas (VMH, LHA and PVN respectively), that contribute to the regulation of food intake are also involved in the regulation of blood glucose and plasma free fatty acid (FFA) levels. This regulation is controlled both directly via neural pathways and indirectly by hormones, e.g., insulin, glucagon, norepinephrine (NE) and epinephrine (E). A description is presented of the intrahypothalamic connections and the pathways between the hypothalamus and the motor areas of both the sympathetic system in the spinal cord (the intermediolateral column IML) and the parasympathetic system in the brainstem (the dorsal motornucleus of the vagus and the nucleus ambiguus). Noradrenergic stimulation of the LHA, VMH and PVN can alter blood glucose, plasma FFA and insulin levels independently of each other, e.g., noradrenergic stimulation of the VMH leads to an increase of insulin, glucose and FFA. Exercise induced increases of glucose are suppressed by alpha-adrenergic blockade of the LHA, VMH and PVN. Alpha-adrenergic blockade of the VMH during exercise causes an exaggerated increase of plasma FFA whereas alpha-blockade of both the LHA and PVN does not change the normal exercise induced increase of plasma FFA. The apparent contradiction that both adrenergic stimulation and adrenergic blockade of the VMH result in an increase in FFA may be explained by assuming postsynaptic alpha- and beta-adrenergic receptors in the VMH controlling glucose and FFA release respectively and FFA release and presynaptic inhibitory alpha-adrenergic receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Immediate and long-term effects of opiate antagonists on postictal behaviour following amygdala kindling in the rat.

Male Wistar rats implanted with bipolar electrodes in the amygdaloid complex were kindled. Subcutaneous injection of naloxone or naltrexone in low doses--0.12 and 0.24 mg/kg, respectively--dramatically reduced the postictal behavioural depression (BD) at 10 or 60 min. Remarkably, the BD was still reduced one day later. It would appear that the brain mechanisms involved in postictal BD use mu-receptors since BD is quite sensitive to low doses of the preferential antagonists naloxone and naltrexone. The long-term effects, the most novel aspect of these studies, are probably related to immediate effects but could be produced through slow genomic processes or alteration of the response to endogenously released enkephalins.

Amygdala↗

Hyperprolactinaemia alleviates behavioral alterations of rats with hereditary hypothalamic diabetes insipidus (Brattleboro strain).

Male rats homozygous for hereditary hypothalamic diabetes insipidus (HO) and their heterozygous (HE) and normal (NO) variants (Brattleboro rats) were made hyperprolactinaemic by homografting two adenopituitaries under the kidney capsule. The high water intake and urine output of homozygous diabetic sham-operated rats (sham-HO) were similar to those of homografted HO animals. Also, hyperprolactinaemia failed to change the water intake and urine output of HE and NO rats, as compared to those of heterozygous (sham-HE) and normal (sham-NO) sham-operated animals. Compared to sham-HE and sham-NO animals, sham-HO rats showed a slow acquisition of active avoidance responses, a facilitated extinction of a pole jumping avoidance behavior and a reduced retention of a passive avoidance response. However, an improved performance of acquisition and retention behaviors up to the level of sham-HEs and sham-NOs was observed in homografted HO rats. Hyperprolactinaemia resulted in a reduced responsiveness to electrical footshock in HO, HE and NO animals, and in facilitated acquisition of active avoidance responses in HE and NO rats, but it failed to affect avoidance extinction and retention in the latter variants. These results suggest that the behavioral alterations shown by homozygous diabetes insipidus rats are alleviated by hyperprolactinaemia although high levels of plasma prolactin do not interfere with the mechanisms regulating water intake and urine output. In addition, hyperprolactinaemia affects the behavior of heterozygous and normal variants of Brattleboro strain but in a selective way.

Animals↗

Intracerebroventricular injection of anti-prolactin serum suppresses excessive grooming of pituitary homografted rats.

Rats with endogenous hyperprolactinaemia, as induced by pituitary homografts under the kidney capsule, displayed increased grooming behavior as compared to that of sham-operated animals. Twelve days after surgery, intracerebroventricular injection of anti-prolactin serum (dilution 1:100, 1 microliter) suppressed the excessive grooming of homografted rats. These observations suggest that prolactin from a peripheral source may reach the central nervous system to affect brain mechanisms involved in grooming behavior.

Adrenocorticotropic Hormone↗

Hippocampal kindling: corticosterone modulation of induced seizures.

The effect of adrenalectomy (ADX) and corticosterone replacement was studied on seizures induced by hippocampal kindling. A complex series of changes occurred in after-discharge (AD) and behavioural depression (BD) during the immediate hours after ADX, culminating at day 1 in markedly decreased AD and BD, which returned to normal over the next several days. These changes were normalized after replacement of the ADX group with low doses of corticosterone. It is concluded that the expression and maintenance of hippocampal kindled seizures is under short-term control of corticosterone.

Adrenalectomy↗

Arginine-vasopressin inhibits centrally induced pressor responses by involving hippocampal mechanisms.

Administration of arginine-vasopressin (AVP) or prolyl-leucyl-glycinamide (PLG) into a lateral cerebral ventricle reduced the magnitude of systolic blood pressure increase (pressor response) induced by electrical stimulation of the mesencephalic reticular formation (MRF) in urethane-anesthetized rats. Bilateral destruction of the dorsal hippocampus prevented the action of AVP on the pressor response. However, the effect of PLG was only slightly reduced by hippocampal lesion. Microinjection of AVP in the dentate area of the dorsal hippocampus mimicked the action of intracerebroventricularly administered peptides. The effect of a single injection of AVP lasted at least for 60 min. Neither hippocampal damage nor peptide administrations resulted in changes in mean arterial blood pressure (basal BP). Bradycardiac response accompanied the BP increase during MRF stimulation. Hippocampal damage or intracerebroventricular administration of AVP and PLG failed to affect the cardiac response. Injection of AVP into the hippocampus tended to reduce the magnitude of cardiac responses caused by MRF stimulation. It is suggested that the inhibition by AVP of a pressor response produced by MRF stimulation involves the dorsal hippocampus. The action of PLG or related peptides seems to be, at least in part, through mechanisms not involving the hippocampus.

Animals↗

Corticosterone decreases the efficacy of adrenaline to affect passive avoidance retention of adrenalectomized rats.

Short-term (48h) adrenalectomy (ADX) resulted in a deficit in the retention of a passive avoidance response. An inverted U-shaped dose-response relationship was found following immediate post-learning administration of adrenaline (A). A in a dose range of 0.005 - 5 micrograms/kg s.c. facilitated later retention. While corticosterone (CS) replacement alone had no effect, pretreatment with CS (300 micrograms/kg) was followed by a shift in the dose-response curve of A in ADX rats. Ten thousand times higher doses of A were required to improve retention behavior. Administration of the potent synthetic glucocorticoid dexamethasone failed to affect the responsiveness to A. It is concluded that corticosterone decreases the efficacy by which adrenaline affects later retention behavior of ADX rats. The specificity of corticosterone in this interaction suggests the involvement of the corticosterone receptor system which has its predominant localization in hippocampal neurons.

Adrenal Glands↗

Endocrine influence on disease outcome: experimental findings and implications.

The psychosocial environment may impose stressor effects on animal and man. Adaptation to these environmental changes requires behavioural, autonomic, neuroendocrine, metabolic, etc. processes. The neuroendocrine system plays a key role in the integration of these processes. Experimental evidence obtained in the rat suggests that neuropeptides related to ACTH, endogenous opioids and their fragments, vasopressin, etc., but also oestrogens may selectively influence the form and magnitude of acute cardiac response to emotional stressors. Dichotomies between the behavioural and cardiac responses may occur too. It is suggested that neuroendocrine action on brain mechanisms that are involved in the organization of behavioural and bodily responses to stressors are important in physiological adaptation. Neuroendocrine disturbances (two much or too little neuropeptides and other hormones) may thereby contribute to the outcome of psychosomatic diseases.

Adrenocorticotropic Hormone↗

The behavioural depression of hippocampal kindled rats is attenuated by subcutaneous and intracerebroventricular naltrexone.

Two questions were asked: Does naltrexone attenuate the behavioural depression (BD) in other models of limbic epilepsy besides amygdala kindling? Does intracerebroventricular (ICV) administration produce the same effects as subcutaneous injection, i.e., attenuation of the BD. Male wistar rats with bipolar electrodes implanted bilaterally in the dorsal hippocampus and a metal cannula in the lateral ventricle were kindled through 1 electrode and EEG recorded through the contralateral electrode. Subcutaneous (sc) and ICV naltrexone administration attenuated the BD of hippocampal kindled rats. These results further implicate the brain opioid system in the postictal phase of kindling and possibly epilepsy.

Amygdala↗

Vasopressin prolongs bradycardiac response during orientation.

Adult male rats were implanted with transcutaneous ECG electrodes and habituated to a dark chamber with elevated background noise levels. ECG was recorded prior to, immediately after, and 3 min after sudden elimination of background noise. The orienting response to the stimulus offset was accompanied by transient bradycardia. Neither AVP (1 microgram/rat) nor oxytocin (1 microgram/rat) injected subcutaneously 1 hr prior to testing altered baseline heart rate or the immediate bradycardiac response to stimulus offset. However, AVP, and to a lesser extent oxytocin, prolonged the bradycardia induced by stimulus offset. The results show that neurohypophyseal peptide hormones enhance the cardiovascular component of orienting to stimulus change.

Animals↗

Inhibition of pressor responses induced by electrical stimulation of the mesencephalon by vasopressin and oxytocin.

Receptors for vasopressin are present in blood vessels, kidney and the brain. Earlier studies indicated that the memory and learning effects of vasopressin are exerted via receptor sites in the brain and that the classical hormonal effects in the periphery can be dissociated in the molecule from the central action. Vasopressin also affects blood pressure regulation. Arg8-vasopressin (AVP) and oxytocin upon intracerebroventricular administration reduced the pressor response elicited by electrical stimulation of the rat mesencephalic reticular formation. Desglycinamide-AVP also exerted this effect. Lesion and microinjection studies revealed that the dentate gyrus of the hippocampus may be a site of action of AVP or its active fragments, inhibiting central pressor responses. Oxytocin appeared to act on structures in the vicinity of the fourth cerebral ventricle.

Animals↗

Hippocampal corticosterone receptors and novelty-induced behavioral activity: effect of kainic acid lesion in the hippocampus.

Rats were injected bilaterally in the dorsal and ventral hippocampus with kainic acid (KA) or with artificial CSF and their behavior and brain corticosterone (B) receptor systems were studied. The hippocampal KA injection destroyed part of the pyramidal neurons and of the dentate gyrus neurons. These neurons contain a receptor system for B. At 2 weeks after the KA lesion this B receptor system displays an increase in apparent maximal binding capacity (Bmax) of approximately 25%. The compensatory increase in B receptor concentration is reflected in an increased uptake of [3H]B in cell nuclei of hippocampal slices incubated in vitro with saturating concentrations of the steroid. Administration of a tracer dose of [3H]B shows that labelled steroid can enter in vivo the cell nuclear compartment of the KA-lesioned lobe. The role of B was investigated on novelty-induced behavioral activities of KA-lesioned and sham-lesioned animals in a large open and a small closed field at 10 days after bilateral adrenalectomy (ADX) or sham-ADX which is 14 days after the (sham) lesion. B (300 micrograms/kg rat) was administered s.c. 1 h prior to the test. KA lesion resulted in an increase in exploratory activity and a reduction in grooming and immobility. After ADX the effect of KA on exploration was reduced in the 5 min open field and abolished in the 30 min closed field. ADX animals displayed more grooming behavior (closed-field). B replacement of ADX rats reinstated the exploratory hyperactivity of KA-lesioned rats. On some components of the behavior such as ambulation in open-field and locomotion in closed field, there was even a larger responsiveness to B in the KA-lesioned rats than in the control animals. It is concluded that (1) after KA lesion of receptor containing neurons, the remaining tissue displays a compensatory increase in number of B receptor sites; (2) B is required for full expression of exploratory activity of rats with or without KA lesions; (3) the KA-lesioned rats display a larger responsiveness to B; and (4) the increased number of B receptor sites may underlie the larger responsiveness to B.

Adrenalectomy↗

Oxytocin is a precursor of potent behaviourally active neuropeptides.

An oxytocin fragment which accumulated during the incubation of oxytocin with brain synaptic membranes was chemically characterized as the hexapeptide pGlu-Asn-Cys(Cys)-Pro-Leu-Gly-NH2 [( pGlu4, Cyt6]OXT-(4-9]. This peptide was approximately a hundred times more potent than oxytocin in attenuating memory consolidation as tested in a passive avoidance test situation; the dose-response relationship was bell-shaped. The des-glycinamide derivative [pGlu4, Cyt6]OXT-(4-8) was nearly as active, but showed a linear dose-response relationship. The data indicate that oxytoxin can act as precursor for potent behaviourally active neuropeptides.

Animals↗