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Biomedical subjects

B Sadowski

Publications and source records attributed to B Sadowski.

At least 55 records · Page 3Linked to original sources

Selective breeding of mice for high and low swim analgesia: differential effect on discrete forms of footshock analgesia.

Selective breeding of mice displaying high and low swim-induced analgesia led to the development of two animal lines divergent in the magnitude of analgesic response to swimming. In this study, animals belonging to the seventh generation of both lines were exposed to two temporally different forms of footshock, one of which produced opioid and the other non-opioid analgesia. We found that selective breeding for high and low swim-induced analgesia exerted a striking influence on the magnitude of the opioid-mediated type of footshock analgesia, but was ineffective on that of the non-opioid type.

Animals↗

Inheritance of stress-induced analgesia in mice. Selective breeding study.

Random mated Swiss mice swam for 3 min at 20 degrees C. The animals with less than or equal to 10 s and greater than or equal to 50 s postswim latencies on the hot plate (56 degrees C) were selected as progenitors of low (LA) and high (HA) analgesia lines, respectively. Gradual divergence of latency distributions and postswim hind paw flick latencies between the two lines was observed in successive generations. As shown by the tail flick test applied to the sixth offspring generation, postswim analgesia in the HA line was not only more pronounced but also lasted longer compared to the LA line and the unselected controls. Possible differentiation of the endorphin system activity in the course of selection is discussed.

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Differentiation of neurochemical basis of stress-induced analgesia in mice by selective breeding.

Two selectively bred lines of mice, one responding with high (HA) and the other with low analgesia (LA) to 3 min swims at 20 degrees C were compared with respect to naloxone ability to reverse such swim induced pain threshold elevation. Also, the analgesic effect of morphine was tested in both lines of mice. Naloxone at a dose of 1 mg/kg significantly reduced postswim analgesia determined with hot plate and tail flick tests in HA mice, but was not effective in LA mice. HA mice responded with significant elevation of hot plate threshold to 0.1 mg/kg of morphine hydrochloride, whereas in LA mice comparable level of analgesia developed after 12.8 mg/kg. The data argue for greater involvement of opioid mechanisms in producing analgesia in HA mice than in LA mice, and so for inheritance of endorphin system(s) activity.

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Activation of anti- and pro-nociceptive mechanisms by front paw shock in spinal mice: involvement of humoral factors.

The effect of prolonged, intermittent front paw shock on nociception was studied in two groups of differently spinalized mice. The animals, spinalized so that the dura was left intact to allow free cerebrospinal fluid (CSF) passage, exhibited post-foot shock increase in latencies of spinally-mediated nociceptive reflexes. This anti-nociception was completely blocked by naloxone. A facilitation of nociceptive reflexes was observed in animals in which the spinal cord was ligated together with the dura. The results indicate that: front paw shock in mice leads to activation of supraspinal sites which mediate anti-nociception by releasing substance(s) reaching the spinal cord via the CSF route; single stressors may simultaneously activate both anti- and pro-nociceptive mechanisms.

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Changes in circadian rhythm and suppression of the plasma cortisol level after prolonged stress in the sheep.

Diurnal variations in the plasma cortisol level were studied in anoestrous, pro-oestrous and pregnant ewes subjected to weak electric stimulation of the fore-limbs 9 h daily for 3 consecutive days. In non-pregnant ewes the cortisol level rose on each of the 3 days when the stimulation was applied and then decreased on the day following the stimulation. A similar decrease in plasma cortisol concentrations in pregnant ewes appeared on the second day of footshocking. The acrophase of the circadian rhythm on electrostimulation days was synchronous with the time of application of footshocks; therefore, in stimulated ewes it was significantly accelerated compared to the prestimulatory day. A decrease in the plasma cortisol level in pro-oestrous and pregnant ewes was accompanied by disappearance of its normal rhythmicity. Since a normal plasma cortisol response to exogenous corticotrophin was noted after 3 days of footshocking it seems unlikely that the decrease in the cortisol level after prolonged stress was caused by exhaustion of the adrenal cortex. Some central mechanisms which could account for the biphasic changes in the plasma cortisol level and for disturbances of the hormone diurnal rhythmicity under conditions of prolonged stress are discussed.

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Suppression of food and water intake after intracerebroventricular infusion of morphine and naloxone in rabbits.

The effect of intracerebroventricular infusion of morphine and naloxone on food and water intake was investigated in rabbits. Morphine hydrochloride at a dose of 120, 10 and 5 micrograms produced statistically significant suppression of 24-h food and water intake. The same effect ensued after infusion of naloxone at dose of 120 and 10 micrograms. Postmorphine aphagia was accompanied by a rise in blood free fatty acids and normal glucose levels. No changes were seen after naloxone.

Animals↗

Enhancement of performance for brain stimulation reward after footshock in rats.

Rats bearing electrodes in the anterior forebrain region (AF), lateral hypothalamus (LH) or dorsal raphe (DR) nucleus were trained to press lever for brain stimulation reward. Ten minutes self- stimulation in all these placements produced a lowering of pain sensitivity as assessed by the hot-plate test. Electric footshock administered on 1 s on/4 s off paradigm for 10 min prior to self-stimulation elevated lever pressing rates in AF rats and in part of LH rats, but not in DR rats. The results are discussed in terms of opiate theory of reinforcement.

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Central dipsogenic effect of vasopressin.

The purpose of the present study was to investigate the possible role of vasopressin (ADH) in the control of thirst. With this aim spontaneous water intake (WI) was examined in conscious dogs after 1) electric stimulation in the basal forebrain causing release of ADH, 2) injection of 0.03, 0.05, 0.10, 0.15, 0.30, and 3.00 mU of ADH into the third cerebral ventricle (3rd V), 3) injection of 0.3, 3.0, and 30 mU of ADH into the lateral cerebral ventricle (LV) and injection of 5.0 and 10.0 mU of ADH into the carotid artery (CA). Stimulation through 10 of 16 electrodes located in various structures of the limbic system caused a significant increase in blood ADH, decrease of urine output, increase in renal free-water reabsorption, nonstimulus-bound drinking, positive water balance, and decrease in plasma osmolality (Posmol). Injection of ADH to the 3rd V caused a significant increase in WI. The maximum WI was observed after injection of 0.10-0.15 mU of ADH. Elevation of WI caused a significant decrease in Posmol 1 h after injection of ADH to the 3rd V. Insignificant increases or no changes in WI were observed when ADH was injected into the LV and CA, respectively. The results suggest that ADH may exert central dipsogenic effects.

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The effect of intracerebroventricular infusion of morphine, methionine-enkephalin and D-Ala2-enkephalinamide on body temperature of rabbits.

The effect of intracerebroventricular infusions of two synthetically obtained peptides: Met-enkephalin hydrochloride and D-Ala2-Met-enkephalinamide hydrochloride, and of morphine hydrochloride on rectal temperature was investigated in conscious rabbits. Morphine hydrochloride in a dose of 240 micrograms and D-Ala2-Met-enkephalinamide hydrochloride in doses of 240 and 3000 micrograms produced a hyperthermia which was accompanied by ear vasoconstriction and shivering. No such effect ensued after Met-enkephalin, possibly due to rapid enzymatic degradation of this compound. The concept of opioid involvement in the central thermoregulatory mechanism is discussed.

Animals↗

Double enkephalins.

Basing on the conclusions drawn from the biological activities of previously synthesized enkephalin analogues, a new class of enkephalin analogues named double-enkephalins have been proposed, in which C-terminal amino acid residue is replaced by a second active fragment of enkephalin analogue connected by diamine bridge. Guinea-pig ileum test showed high biological activity of proposed analogues but depending on the size of diamine bridges.

Animals↗

Enhancement of osmotic thirst elicited by electric stimulation of the limbic system in dogs.

Seven dogs were chronically implanted with 30 electrodes directed at various structures of the basal forebrain. Osmotic thirst threshold (expressed as an increase in plasma osmolality and a decrease in cellular water content caused by an intravenous infusion of 5% NaCl, necessary to induce drinking) was measured during electric stimulation of the basal forebrain and compared to that found under control conditions. Stimulation through 11 electrodes located in the lateral part of the septum (5 locations) and other parts of the limbic system markedly decreased the osmotic thirst threshold. The increment in plasma osmolality necessary to elicit drinking decreased from 9.7 +/- 1.3 to 4.8 +/- 1.2 mmol/kg (n = 11). The volume of water drunk at the thirst threshold did not differ significantly. A significant augmentation of the volume of water drunk during 1 h following infusion of hypertonic saline was observed when the infusion was combined with stimulation of the gyrus rectus, precommissural septum and nucleus accumbens. These and previous results (SZCZEPANSKA-SADOWSKA et al., 1979) suggest that the limbic system of the basal forebrain exerts both excitatory and inhibitory influences on the thirst system. The prolonged poststimulatory overdrinking indicates that enhancement of osmotic thirst cannot be entirely explained by an immediate action of the stimulating current on the neurons of the thirst system.

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High performance liquid chromatographic assay of dexamethasone in plasma and tissue.

Dexamethasone in plasma and in tissue is specifically quantitated by high performance liquid chromatography (ultraviolet detection at 254 nm) with an octadecyl silane reversed-phase chromatographic column employing peak-height ratio determination (internal standard, cyheptamide). The sample is first washed with heptane under alkaline conditions. The dexamethasone is then extracted from the washed sample with dichloromethane containing the internal standard. Dichloromethane is evaporated to dryness, and the concentrated extract is dissolved in tetrahydrofuran and then injected into a high performance liquid chromatograph. Dexamethasone and internal standard are eluted with a mixture of acetic acid, methanol, butanol, and water (11/19/30/440 by volume). Sensitivity limit is 10 ng, with linear response to at least 1.000 mg/liter plasma. Analytical recovery of dexamethasone from plasma is almost complete, and approximately 87% dexamethasone is recovered from brain tissue. Intra-assay precision (CV) is 1.07% (N = 11), and interassay precision is 1.38% (N = 5). No interference occurred in plasmas from patients treated with various drugs other than dexamethasone. Dexamethasone was estimated in plasma and in tumor tissue from patients on dexamethasone therapy.

Administration, Oral↗