Biomedical subjects

B Dubrovsky

Publications and source records attributed to B Dubrovsky.

At least 19 recordsLinked to original sources

PubMed1991

Pelvic floor muscles response to graded rectal distension and cutaneous stimulation.

The responses of the external ani sphincter (EAS) and the levator ani (LA) muscles to graded rectal distension and to cutaneous and genital stimulation were examined in 25 cats of either sex. The animals were anesthetized with sodium pentobarbital (30 mg/kg, intraperitoneal) and then tested in two positions: with hindlimbs extended and with hindlimbs flexed simulating the straining position. Graded rectal distension was performed at two speeds: 1 and 10 sec. Basal levels of activity in the EAS were higher in the straining than in the extended position (P less than 0.005). The EAS responded to rapid rectal distension with inhibition of its activity. When changed to the straining position significant increases in muscular activity were observed after 35 cc of balloon insufflation (P less than 0.005). In the same muscle, slow distension produced an initial decrease in activity followed by significant increases after insufflation of 40 cc in the extended position and of 30 cc in the straining position. Basal activity in the LA was similar in both positions tested. The main effects of rectal distension in this muscle were increases in activity, significant only after high volumes of air inflation in the straining position (P less than 0.0001). Cutaneous stimulation disclosed a receptive field that was widespread for the EAS, extending over lumbosacral dermatomes (L3-S2), but greatly restricted for the LA. Responses to vaginal and cervical stimulation were more reliably obtained from the LA (P less than 0.001). These differences indicate that the EAS and LA muscles of the cat correspond with distinct, although related neural circuits.

Animals↗

PubMed1991

Adrenal steroids and the physiopathology of a subset of depressive disorders.

Patients suffering from Cushing's disorders (syndrome and disease) are significantly affected by psychological disturbances that overlap with depressive disorders. In turn, a subset of patients with affective disorders present with hypercortisolemia, and non-suppression in the Dexamethasone Suppression Test (DST). We have shown that long-term potentiation (LTP), a putative memory mechanism, is significantly affected by steroids when tested on the hippocampus, a crucial structure for memory processes. We propose that an imbalance of adrenal steroids and their metabolites, interacting at the level of the hippocampus, play a fundamental role in the psychophysiopathology of Cushing's and depressive disorders. By biasing memory mechanisms, the imbalance of these hormones sets both distorted mood, and hence memory contents, and distorted cognition based on recollection and present experiences.

Adrenal Cortex Hormones↗

PubMed1991

Modulation by adrenal steroids of limbic function.

The effects of various steroid hormones on the long-term potentiation (LTP) of the rat hippocampus were evaluated. LTP was elicited in the dentate gyrus of adrenalectomized animals with priming tetanic stimulation (200 Hz-0.03 cps) of its main afferent, the perforant pathway. Single pulse EPSP (excitatory post-synaptic potential) slope, and PS (population spike) amplitude values were compared before and after the i.v. injection of the hormones and subsequently after the priming stimulation every 15 min up to 1 h. 18-OH-deoxycorticosterone (18-OH-DOC) produced a significant decrease of the EPSP LTP and arrested the PS enhancement in comparison with vehicle at every time post-tetanic stimulation. Its 21-acetate derivative produced a moderate decrease of the EPSP and had no effect on the PS LTP in comparison with vehicle. Deoxycorticosterone (DOC) exhibited similar effects on the EPSP although less marked than with 18-OH-DOC while the PS only decreased in the first 30 min post-train. Corticosterone decreased both EPSP and PS for the first 15 and 30 min after priming stimulation, respectively, matching values with those of vehicle afterwards. Its 21-acetate produced an initial decrease of the EPSP and had no effect on the PS LTP. Allo-tetrahydro-DOC produced little, if any, initial enhancement of the PS LTP in comparison with vehicle. These results show that the adrenal steroids tested can modulate hippocampal LTP, a plastic phenomenon in the mammalian CNS which is known to be related to memory and learning processes. Moreover, adrenal steroids can independently modify the PS or EPSP components of the LTP, suggesting different loci of action at the neuronal level.

Adrenal Glands↗

PubMed1991

Effects of adrenal steroids and their reduced metabolites on hippocampal long-term potentiation.

We studied the effects of steroid hormones on the hippocampal long-term potentiation (LTP), a putative mechanism of neuronal plasticity and memory storage in the CNS. In vivo experiments were performed in rats under chloral hydrate anesthesia (0.4 mg/kg i.p.). All animals were adrenalectomized 48 h before recording. LTP was induced after priming tetanic stimulation at the perforant pathway (PP) and single pulse field potentials were obtained from the dentate gyrus (DG). The excitatory post-synaptic potential (EPSP) slope and population spike (PS) amplitude were analyzed before and after the i.v. injection of the steroids and after the induction of LTP, and followed up to 1 h. Results obtained with the hormones were compared with matched control animals injected with vehicle alone, Nutralipid 10%. Previous results from our laboratory showed that deoxycorticosterone (DOC) decreased the magnitude of the EPSP at all times after priming stimulation and the PS decreased during the first 30 min of the LTP. Corticosterone decreased the EPSP in the first 15 min and the PS during the first 30 min after priming stimuli. In these experiments the mineralocorticoids aldosterone and 18-OH-DOC elicited a decrease of the EPSP at all times post-train; and no significant difference against vehicle was observed in the PS. Post-injection values were not changed except for 18-OH-DOC at a dose of 1 mg, where a decrease of both the EPSP (P less than 0.01) and the PS (P less than 0.02) was observed against vehicle. ATH-progesterone at 0.1 mg/rat also decreased the EPSP values significantly after priming stimulation and no significant changes against vehicle were observed in the PS. These results show that adrenal steroids can modulate hippocampal LTP, that they can act at different neuronal loci and with different time courses in the development of the phenomena.

Adrenal Glands↗

PubMed1990

Early and late effects of steroid hormones on the central nervous system.

Steroids have fast and probably partly GABA-mediated central anaesthetic effects for which a strict structure-function correlation is required. They also affect short- and long-term activity in the CNS in other ways. One of these is long-term potentiation (the persistent facilitation of synaptic transmission), which occurs particularly in the hippocampus after repetitive stimulation of a fibre pathway. Two clearly distinguished components of the evoked response can be studied in the hippocampus: the excitatory postsynaptic potential (EPSP) which denotes the graded depolarization of the somadendritic region of the neuron and the population spike (PS), a manifestation of the all-or-none discharge of the cell action potential. Corticosterone had a significant depressant effect on the EPSP component of the evoked response immediately and 15 min after injection. Thereafter EPSP amplitudes were within normal values. Corticosterone significantly decreased the PS immediately after the train, the component remaining low 30 min after the train. 5 alpha-Dihydrocorticosterone (a ring A-reduced metabolite of corticosterone) significantly reduced the PS component of the response at all times after injection. 18-Hydroxydeoxycorticosterone and deoxycorticosterone significantly decreased both EPSP and PS components of the evoked response from the time of infusion. Contrary to expectation, tetrahydrodeoxycorticosterone was ineffective in decreasing, and if anything, enhanced the development of long-term potentiation. 18-Hydroxydeoxycorticosterone 21-acetate behaved like vehicle, except for the first 30 min after injection, when the EPSP was decreased. Different steroids can selectively affect different parts of a neuron and appear to show a different structure-function correlation for long-term potentiation from that required for anaesthesia.

18-Hydroxycorticosterone↗

PubMed1990

Neurobiological aspects of the pelvic floor muscles involved in defecation.

Neurobiological aspects of the organization of pelvic floor musculature are reviewed. Evolutionary considerations on the origin of these muscles indicate that they develop with specific attachments and function, i.e., do not derive from preexisting muscles such as the ones from the tail. Anatomically, pelvic floor muscles can be divided into 1) true sphincters and related muscles and 2) muscles which flank the visceral outlets. While in quadrupedal mammals the EAS behaves as a fast twitch muscle, in man this muscle has slow twitch characteristics. Like some epaxial muscles the EAS has a strong connectivity with its surrounding skin. In further analogy with some epaxial muscle the EAS, although endowed with muscle spindles, is devoid of the phasic, monosynaptic component of the stretch reflex. Onuf's nucleus which innervates pelvic floor muscles receives an important group of suprasegmental afferents including, probably, direct corticospinal fibers. Pelvic floor muscles play a fundamental role in signaling arrival of feces to the perineum. While sphincteric activity is important for continence, other mechanisms such as the anorectal angle and anal cushions are also of relevance. Although emphasis has been put on motor factors, fecal incontinence can also result from impairments in sensory mechanisms of the anorectal system. In diseases like amyotrophic lateral sclerosis, Werdnig Hoffman's and others there is selective sparing of neuropathology in Onuf's nucleus. In contrast, the nucleus is affected in some autonomic visceromotor neuronal disorders, e.g., Shy Drager syndrome, Fabry's disease. It has been suggested that Onuf's nucleus occupies an intermediate position between visceral and somatic nuclei.

Animals↗

PubMed1989

Apomorphine: clinical studies on erectile impotence and yawning.

1. The erectile response to the short-acting dopamine (DA) receptor agonist, apomorphine (Apo) HCl (0.25, 0.5, 0.75 and 1.0 mg sc), and placebo was evaluated in 28 impotent patients and penile circumference monitored using a mercury strain gauge and strip chart recording. 2. A full erection (increment in penile circumference greater than 2 cm and lasting at least one minute) occurred in 17 patients with Apo; no erection developed after placebo. An erection occurred in 6/8 patients with impaired glucose tolerance, 2/6 patients with diabetes mellitus and in both patients on lithium. 3. Nine patients who responded to Apo were treated in an open trial with bromocriptine; 6 reported improvement in potency. 4. Impairment in DA function may play a role in idiopathic impotence and in impotence associated with impaired glucose tolerance and diabetes mellitus. 5. An erectile response to Apo may predict therapeutic response to bromocriptine or other long acting dopaminergic agents. 6. Lithium, which inhibits DA-sensitive adenylate cyclase, does not prevent Apo-induced erections. This provides further support indicating that Apo induces erections by an effect on D2 receptors. 7. The yawning response to placebo and four doses of Apo HC1 (3.5, 5.0, 7.0, and 10.5 ug/kg sc) was evaluated in five normal men using a polygraphic technique. The yawning response was also assessed in normal young (less than 30 yrs; N = 16) and elderly (greater than 60 yrs; N = 12) volunteers. 8. Under experimental conditions of study, placebo induced spontaneous yawning. This was antagonized by 3.5 and 5.0 ug/kg Apo HC1 but increased by 7.0 ug/kg Apo HC1. These observations are compatible with the view that Apo HC1 in doses of 3.5-5.0 ug/kg stimulates presynaptic DA receptors whereas 7.0 ug/kg stimulates postsynaptic DA receptors. 9. Spontaneous and Apo-induced yawning were significantly decreased in the elderly which suggests that D2 receptor function declines with normal aging.

Adult↗

PubMed1988

Effects of rectal distension on the sphincter ani externus and levator ani muscles in cats.

The response characteristics of levator ani (LA) muscles to rectal distension and its rectified and integrated EMG activity was recorded and compared with the responses of the sphincter ani externus (SAE) to the same stimuli. Experiments were performed in 42 cats anesthetized with chloralose (70 mg/kg) dissolved in a 25% urethan-saline solution. Fast (about 1-2 s) rectal distension (10-40 ml of air were injected into a rubber balloon in the rectum, reaching pressures of up to 80 mmHg) produced a reflex contraction of both LA and SAE muscles. Sustained distension elicited a sustained discharge from the LA muscles that endured for the duration of the distension, up to 2-3 min. These changes were observed in 75% of 210 trials. EMG activity increased from 30 to over 600% of base-line levels, with the majority, 65% of trials, showing greater than 100% increase. In contrast to these excitatory responses of the LA muscles, SAE responded to sustained rectal inflation with inhibition of ongoing activity, an inhibition that could reach muscular silence. Fast intermittent distension, one every 2-3 s, however, produced an increase in the level of activity of the SAE. Analysis of the EMG activity preceding defecation revealed an increase of LA activity 1-2 min before actual expelling. We believe this result to be consistent with the hypothesis that these muscles may contribute to anorectal evacuation. In the anesthetised animal, during the passage of solid material through the anus, the SAE showed increased activity. We believe this to be the result of a local phenomenon, the development of a tonic stretch reflex in the SAE.(ABSTRACT TRUNCATED AT 250 WORDS)

Anal Canal↗

PubMed1987

Ventral root potentials of the cat's sacrococcygeal segments evoked by stimulation of intact and transected dorsal roots.

The latency and amplitude of reflex-evoked potentials in the sacrococcygeal ventral roots of acute spinalized cats were investigated. The characteristics of the potentials were examined in response to electrical stimulation of intact and acutely transected dorsal roots. We found that: the last sacral and caudal (coccygeal) segments of the cat's spinal cord are endowed with electrophysiologic characteristics that distinguish them from other spinal segments (e.g., L7-S1); afferent stimulation of the corresponding intact dorsal roots evokes in the ventral root of segment S2 a small monosynaptic response, whereas no monosynaptic response is seen in segment Ca6; acute transection of the dorsal roots provokes an increment of the monosynaptic response in all segments studied except for Ca6; rhizotomy provokes in Ca5 the appearance of polysynaptic responses to electrical stimulation of the corresponding dorsal root; and transection of the cutaneous afferent fibers of the coccygeal motoneurons resulted in an increment of monosynaptic and polysynaptic responses, indicating the removal of inhibitory effects.

Animals↗

PubMed1987

Reflex responses evoked from cats' coccygeal ventral roots by electrical stimulation of the tail nerves.

In the terminal cone of the cat spinal cord, the coccygeal segments give rise to the ventrolateral and dorsomedial nerves of the tail. Extracellular recording was made from the ventral root of the coccygeal segments after stimulation of each or both ventrolateral and dorsomedial nerves. Stimulation of either nerve caused a polysynaptic response of 5- or 10-ms latency. A monosynaptic response was not seen unless posttetanic potentiation was carried out, or both nerves were stimulated simultaneously. It is suggested that the ventrolateral and dorsomedial nerves are linked by a common pathway, allowing spatial summation to take place, thus facilitating the elicitation of a monosynaptic response. The neural organization underlying the muscle movements of the cat's tail is discussed.

Animals↗

PubMed1987

A simple method for the study of yawning in man induced by the dopamine receptor agonist, apomorphine.

Apomorphine (Apo), a dopamine (DA) receptor agonist, induces yawning by stimulating central DA autoreceptors. Few data are available on Apo-induced yawning in man. A simple method for recording and measuring Apo-induced yawning by measuring the displacement of the lower jaw using a pair of linearlized magnetometers with one sensor attached to the forehead just below the hairline and the other under the chin is described. The output of the magnetometers is fed into a DC amplifier and displayed on a strip chart recorder. Complete concordance between evaluators reading the tracings and between observed yawning and recorded yawns was found. Measuring Apo-induced yawning may provide a simple approach to evaluating DA autoreceptor function in normal subjects and in patients with psychiatric and neurological disorders. Preliminary data show that Apo-induced yawning is more marked in women than in men. This is in contrast to spontaneous and drug-induced yawning in animals which is predominantly a male phenomenon. Sleep appears to inhibit Apo-induced yawning.

Apomorphine↗

PubMed1987

The effect of progesterone and its metabolites on the interictal epileptiform discharge in the cat's cerebral cortex.

The antiepileptic effect of progesterone, 5-alpha-pregnane-3,20-dione, 3-alpha-hydroxy-5-alpha-pregnane-20-one, and 3-alpha-hydroxy-5-beta-pregnane-20-one were tested in an experimental animal model, and compared with the effect of clonazepam. The steroids were dissolved in serum from ovariectomized cats. Ovariectomized adult cats were used and spontaneous epileptic discharges were generated by placing small pieces of penicillin-soaked filter papers on the ipsi and contralateral cerebral cortex. The frequency and amplitude of the interictal epileptiform spikes were recorded, and analysed in a computer. The changes in frequency and amplitudes were calculated. The drugs were infused during 20-s periods into one cerebral hemisphere via the ipsilateral lingual artery with speeds of 1.1, 3.4 and 6.3 ml min-1. A penicillin focus on the contralateral hemisphere served as a simultaneous control. Progesterone and clonazepam showed similar inhibitory effects on epileptiform interictal spiking (median reduction of spike frequency 21%, cf. Table I). The 5-alpha-pregnane-3, 20-dione was generally less potent than progesterone (median reduction 9%) and the 5-alpha- and 5-beta-pregnanolones were two to three times more potent than progesterone (54-66% reduction). The latency of the inhibitory effect was 4-10 s measured from the entrance of the infusion into the lingual artery. The depression lasted 10-20 min. It is concluded that the pregnanolones have strong antiepileptic properties. The rapid onset of effect indicates that the steroids may interact with the neuronal function at the membrane or synaptic levels.

5-alpha-Dihydroprogesterone↗

PubMed1986

Effects of 18-hydroxydeoxycorticosterone on central nervous system excitability.

The effects of 18-hydroxydeoxycorticosterone (18-OH-DOC) on central nervous system excitability were studied in adrenalectomized rats. Sixty-four evoked potentials (EP) recorded from the pontine reticular formation were averaged before and after the injection of vehicle and hormone. 750 micrograms of 18-OH-DOC dissolved in 0.5 ml of a 4:1 saline Cremophor-EL solution were injected i.v. A decrease of 55.7 +/- 6.1% in the amplitude of the EPs was observed with the hormone 16.3 min +/- 2.7 (SE) after injection. Amplitude values returned to baseline levels 38 min +/- 6.8 (SE) after injection. The secretion of 18-OH-DOC is greatly increased by ACTH and might modulate central nervous system function.

18-Hydroxydesoxycorticosterone↗

PubMed1986

Differential roles of raphe nuclei in the regulation of dopamine beta-hydroxylase in the adrenal gland of the rat.

The effect of reserpine on the activity of dopamine beta-hydroxylase (DBH) in the adrenal gland of the rat was determined following electrolytic lesion of the dorsal raphe nucleus (DRN) or medial raphe nucleus (MRN). In sham-operated rats, as well as in those with a lesion of the DRN, there was no significant modification of the action of reserpine on this enzyme. However, a lesion of MRN potentiated the inducing action of the drug. A specific role of MRN in the serotonergic regulation of adrenal DBH is suggested by this work.

Adrenal Glands↗

PubMed1985

Effects of corticosterone and 5 alpha-dihydrocorticosterone on brain excitability in the rat.

The effects of corticosterone (B) and its reduced metabolite 5 alpha-dihydrocorticosterone (DHB) on CNS activity in the rat were examined. Two indices of brain excitability were evaluated: 1) amplitude of population responses (evoked potentials [EP] to sciatic nerve stimulation) and 2) changes in the rate of firing of tonically discharging neurons--both at pontine brainstem regions of the reticular formation. Experiments were carried out in adrenalectomized rats, and recordings were obtained from animals under urethane anesthesia. Steroids were dissolved in a 4:1 saline:Cremophor-El (Sigma) solution and doses of 750 micrograms/0.5 ml were injected (IV). The effects of B on EPs were bidirectional. Increases (8 animals) and decreases (6 animals) of the amplitude responses in different animals were observed. In 4 animals, no changes were detected. In contrast, injection of DHB produced a consistent and significant reduction of brainstem sciatic evoked potentials in 10 of 12 animals tested; 2 animals did not respond to the steroid. At the neuronal level, the effects of the steroids were evaluated by the changes they induced in the mean firing frequency (P less than 0.01) measured during 5-min intervals as determined by a one-way analysis of variance and analysis with a test of multiple comparisons. Only cells that fired in a stationary mode for 15 min before the steroid injection were studied. A more consistent pattern of responses to B was observed at the single-cell level. From 31 neurons that responded to the hormone, of 76 examined, 27 showed an increase in their firing rate and only 4 neurons showed a decrease. The increase in firing rate had an onset latency of 2-5 min (means = 3.5, SE 0.43) with a duration of 16-25 min (means = 17.5, SE 2.7). Of 69 neurons that were tested with DHB, 51 showed a significant decrease in their mean firing frequency. Onset latency of the effect was 2-8 min (means = 4.0, SE 1.21) and the duration of the induced changes was 16-40 min (means = 30.0, SE 3.47). Central interactions of DHB and B when sequentially administered were examined in 28 neurons. Of these, 21 responded to DHB administration with a significant decrease in their firing rates. In 11 of these neurons, injection of B, 5 min after DHB, was followed by a rapid (1-2 min) return of the neurons to baseline firing rates.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

PubMed1985

Spinal control of pelvic floor muscles.

A prevalent notion in the literature is that the pelvic floor muscles behave as a unitary mass. We examined this proposition experimentally. In spinal cats, we recorded EMG activity from the following pelvic floor muscles: the sphincter ani externus (SAE), the abductor caudae internus (coccygeus), and the levator ani (pubiocaudalis) muscles. The epaxial sacrocaudalis dorsalis lateralis muscle was also exposed and prepared for recording. Electrical stimulation of S2 ventral roots elicited twitch responses of the sphincter ani externus and of the sacrocaudalis dorsalis lateralis muscles. Stimulation of S3 and Cx1 ventral roots elicited responses in the other two muscles studied, the levator ani and abductor caudae internus. Thus a clear segregation of the segmental motor neuron pools innervating the different pelvic floor muscles was demonstrated. The various muscles of the pelvic floor region could be reflexly activated either individually or as a mass unit depending on the intensity of stimulation. Tactile or electrical stimulation of pudendal regions on either side of the body elicited responses of the sphincter ani externus. In contrast, activation of the levator ani and abductor caudae internus muscles could be lateralized: tactile or electrical stimulation of the dorsolateral surfaces at the base of the tail region elicited ipsilateral responses from these muscles. Section of one pudendal nerve did not alter the level of tonic activity (2 to 4/s) of the sphincter ani externus. However, bilateral section of the pudendal nerve entirely abolished both tonic activity and phasic responsiveness of the SAE without affecting the activity of the levator ani and abductor caudae internus muscles. Pudendal nerve stimulation elicited only polysynaptic reflex responses from S2 ventral roots. The results presented show that the neural apparatus of the striated musculature of the pelvic floor is capable of activating individually the different muscles that make up the system, and that the sphincter ani externus from one side, and muscles that conform the diaphragm pelvis from the other, are subserved by different neuronal circuits.

Animals↗

PubMed1985

CNV and time estimation.

We investigated the hypothesis that the development and resolution of CNV waves may, in part at least, reflect time estimation processes in the nervous system. Specifically, we postulated that subjects with a high degree of accuracy in time estimation tasks will show a fast resolution of the negativity following the imperative stimulus (S2). The results showed that, consistent with the hypothesis, accurate estimators, as a group, show CNVs with faster resolution of negativity after S2. In addition, they have CNVs of lower amplitude and show a slower rise time to peak negativity than subjects with poor time estimation abilities.

Adult↗

PubMed1984

A simple open-loop vibrating system for variable amplitude and frequency sinusoidal stretching of muscles.

A device designed to provide controlled variable amplitude and frequency sinusoidal stretching of muscles is described. The constructed vibrator included a pivoted lever with one arm fixed and the other variable, and was driven by an electric motor. The use of a powerful motor ensured that the stimulation parameters would not be significantly affected with tension changes in the muscle during contraction, which enables operating the system in an open-loop mode. This device is simple, low cost, and may be used in a variety of neurophysiologic studies with only conventional grounding, shielding, and noise suppression.

Animals↗