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G J Kant

Publications and source records attributed to G J Kant.

At least 37 records · Page 2Linked to original sources
PubMed1991

Effects of MK-801 on learning and memory as assessed using a novel water maze.

The effects of the NMDA receptor antagonist MK-801 [(+)-10,11-dihydro-5-methyl-5H-dibenzo [a,d]-cyclohepten-5,10 imine hydrogen maleate] on learning and memory were assessed using a water maze. The maze was a traditional type of maze with alleys and choices between various paths, but set inside a pool of water to a height of 25 cm. Different mazes could be configured by altering the arrangement of open vs. closed doors. Both the time required to reach an out-of-the-water exit platform and the errors made during the swim from start to finish were recorded. Learning was assessed during the first 10 to 20 trials in a new maze configuration, while memory was tested after the maze was well learned. Three experiments, some with several phases, were performed. These experiments compared the effects of 0.1 mg/kg of either (+)-MK-801, or (-)-MK-801 vs. saline on learning new maze configurations as well as swimming well-learned mazes. Neither of the MK-801 isomers impaired performance of a previously learned maze. (+)-MK-801 clearly slowed learning of new mazes as measured by both maze completion time and errors committed, while (-)-MK-801 had a significant but smaller effect on learning. Rats given (+)- or (-)-MK-801 (0.1 mg/kg) for 16 days while learning one maze and then challenged to learn a new maze without drug administration performed no differently on the new maze than controls, suggesting that the acute effect of MK-801 on learning is not long lasting.

Animals↗
PubMed1990

Rat maze performance after resuscitation with cross-linked hemoglobin solution.

Unmodified stroma-free hemoglobin has been found to produce neurotoxicity and behavioral impairment in rats. In contrast, a recent assessment of a modified (diaspirin alpha-alpha cross-linked) hemoglobin (HbXL) solution found normal memory, learning, and brain histology after infusion of a clinically relevant dose of a 14% HbXL solution. The current study examined this potential resuscitation fluid for evidence of neurobehavioral toxicity under clinical conditions. Rats were trained to complete a water alley maze, had 50% of their total blood volume (30 ml/kg) withdrawn, were resuscitated with 14% HbXL solution (45 ml/kg), Ringer's lactate (60 ml/kg), or autologous shed blood, and were subsequently retested in the water maze. Rats resuscitated with HbXL or autologous shed blood survived resuscitation, while 20% of those resuscitated with Ringer's lactate died during treatment. No significant performance degradation was observed in the HbXL rats following resuscitation, and no brain pathology was observed at necropsy 10 days after treatment. Ischemic brain lesions were observed in three (25%) of the surviving rats resuscitated with Ringer's lactate solution. Renal tubule regeneration indicative of an earlier insult was observed in animals from all three groups. A significant correlation between the total pathology in the five organs examined and maze errors was observed (p less than 0.001). The survival, maze performance, and histology results suggest that resuscitation with 14% HbXL solution does not cause neurotoxicity, as assessed in this lethal hemorrhage model.

Animals↗
PubMed1989

Dexamethasone suppresses ACTH release without attenuating pituitary cyclic AMP response to stress in vivo.

Dexamethasone, a synthetic glucocorticoid, has been shown to decrease basal and stress-elevated levels of the pituitary hormone ACTH. Glucocorticoids are known to bind to multiple sites within the brain and pituitary and it is not known which site(s) is most important in mediating the observed inhibition of ACTH release. At the level of the corticotroph, there is contradictory data from in vitro studies regarding whether dexamethasone acts proximal or distal to the formation of the cyclic AMP second messenger that has been shown to be involved in CRF-stimulated ACTH release. In the present report, we have examined the effects of dexamethasone pretreatment on stress-induced elevations in pituitary cyclic AMP and the release of ACTH in vivo. Acute stress (15 min of intermittent footshock) elevated levels of pituitary cyclic AMP and plasma ACTH consistent with previous studies. Dexamethasone administration (0.4 mg/kg 24 hr prior to sacrifice plus 0.2 mg/kg 2 hr prior to sacrifice) inhibited stress-induced elevations in plasma ACTH but did not affect pituitary cyclic AMP response to acute stress. These findings suggest that dexamethasone inhibits the release of ACTH via an action distal to the generation of cyclic AMP.

Adrenocorticotropic Hormone↗
PubMed1989

ACTH, prolactin, corticosterone and pituitary cyclic AMP responses to repeated stress.

The present experiment was conducted to determine whether the plasma hormonal and pituitary cyclic AMP responses observed following a single exposure to an acute stressor would diminish following reexposures to the same stressor. Fifteen-min stress exposures (forced running) were separated by 45-min recovery periods. Separate groups of control and stressed animals were sacrificed before and after each of four 15-min stress periods and after each recovery period. The first exposure to 15 min of forced running raised plasma ACTH, corticosterone and pituitary cyclic AMP levels approximately 6-fold and more than tripled levels of plasma prolactin. Plasma ACTH and pituitary cyclic AMP responses to the second, third and fourth stress exposures were very similar to the responses to the first stress exposure, and levels of these substances returned to prestress levels during each 45-min recovery period. Plasma prolactin responses to the four stress sessions were somewhat variable but no significant trend among the responses was seen. Plasma prolactin levels also returned to prestress levels between stress exposures. Corticosterone levels were similar following each of the four stress sessions but levels remained elevated compared to prestress levels between stress exposures. These data suggest that pituitary responses to acute stress are rapid, that return to prestress levels is also rapid, with the exception of corticosterone, and that repeated responses of the same magnitude may be evoked when stressors are separated by short recovery periods.

Adrenocorticotropic Hormone↗
PubMed1989

Effects of adrenalectomy on CRH regulation of ACTH release: adenylate cyclase activity, cyclic AMP-dependent protein kinase activity and ACTH release.

Corticotropin releasing hormone (CRH) stimulation of ACTH release and cyclic AMP-mediated events involved in the control of ACTH release were compared in sham-operated and adrenalectomized rats. CRH-stimulated adenylate cyclase activity was decreased in pituitary homogenates from adrenalectomized animals. CRH-stimulated cyclic AMP accumulation was essentially abolished and CRH-stimulated cyclic AMP-dependent protein kinase (A-kinase) activity was decreased in freshly prepared anterior pituitary cells from adrenalectomized animals. Basal and CRH-stimulated ACTH release was elevated in these cells. Since ACTH release is increased in adrenalectomized rats despite the down regulation of CRH-linked pituitary mechanisms, we speculate that the site of action of disinhibition by corticosterone of ACTH release (or synthesis) following adrenalectomy is distal to the generation of cyclic AMP and/or that non-CRH mediated mechanisms assume a greater role in ACTH regulation following adrenalectomy.

Adenylyl Cyclases↗
PubMed1989

Rat maze performance after infusion of cross-linked hemoglobin solution.

Neurotoxicity and behavioral performance degradation have previously been observed in rats after exchange transfusions with unmodified stroma-free hemoglobin solutions. We evaluated a diaspirin cross-linked stroma-free hemoglobin solution (HbXL) for evidence of neurotoxicity. Rats that were trained to complete a water alley maze received a clinically-relevant dose (20 ml/kg) of the 14% HbXL solution on top of their normal blood volume. After post-treatment memory testing in the water maze, the same rats were challenged to learn an elevated radial-arm maze. The HbXL and control groups showed no water maze performance degradation after treatment, and all groups demonstrated learning of the radial-arm maze as shown by decreased errors and times to completion. The brains, heart, and livers presented normal histology thirty days after infusion, but six of fifteen animals showed marked renal tubular regeneration. The normal memory and learning performance and brain histology after infusion with HbXL suggests that this hemoglobin solution is not neurotoxic to unhemorrhaged rats.

Animals↗
PubMed1988

Psychological stress increases pituitary cyclic AMP.

Exposure to physical stressors has been shown to produce increases in pituitary cyclic AMP in laboratory rats. In this experiment, the generality of these findings has been extended to include a psychological stressor, defined as returning the animals to a situation in which they had been exposed to footshock for four days. Rats in the psychological stress group exhibited increases in pituitary cyclic AMP and in plasma corticosterone and prolactin which were similar to those seen in animals that received the physical stressor on the test day. At present it is not known whether the effects are due to associative conditioning or to sensitization of the neuroendocrine system following repeated presentations of the physical stressor.

Animals↗
PubMed1988

Maze performance: a direct comparison of food vs. water mazes.

The purpose of these experiments was to evaluate the utility of a water maze for testing performance in nonfood-restricted rats. Water maze performance was compared to performance in a food-rewarded (food) maze. Separate groups of rats were given single daily trials of 34 days in one of two mazes. The path through each maze was identical; in fact, the same maze was used with the exception that the maze was filled with water during water maze testing and left dry during the food maze testing. In the food maze, a chocolate peanut butter chip was placed at the finish. In the water maze an out-of-the-water platform was placed at the finish. The time to reach the finish was measured for each trial. Both free-feeding and food-restricted rats were tested in each maze. Free-feeding rats learned the food maze with great difficulty, requiring more than 30 trials. Food-restricted rats learned the food maze more quickly than did free-feeding rats. Free-feeding rats learned to solve the water maze more quickly than the food maze. Food-restricted rats also learned the water maze more quickly than the food maze and learned both mazes faster than free-feeding rats. Plasma levels of corticosterone, ACTH and prolactin were measured in all rats immediately following completion of the last maze trial. Plasma corticosterone levels were elevated and plasma prolactin levels were decreased in both food-restricted groups as compared to free-feeding rats, demonstrating that food restriction was chronically stressful.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1988

Long-term sequelae of soman exposure: hormonal rhythms two weeks postexposure to a single dose.

Two weeks following a single exposure to either soman (100 micrograms/kg, sc) or saline, rats were sacrificed at 2-hr intervals over a 26-hr period. Trunk blood was collected and plasma was stored until assayed for corticosterone, prolactin, growth hormone, adrenocorticotropin, beta-endorphin, and beta-lipotropin. Rats surviving for 2 weeks following soman appeared well groomed and were gaining weight at a rate similar to saline-treated rats at the time of termination. Thus, they appeared to have recovered from the initial physiological effects of soman exposure. However, substantial differences in plasma levels of most hormones were seen in comparing soman- vs saline-treated rats. Levels of prolactin were suppressed at all time points in soman-treated rats. Growth hormone secretion was also suppressed and the normal episodic peaks of growth hormone were missing in soman-treated rats. Both soman- and saline-treated rats displayed circadian rhythms in levels of plasma corticosterone, but the usual late afternoon rise in plasma corticosterone levels was shifted to earlier time points in the soman-treated rats. Levels of beta-endorphin and beta-LPH were slightly but significantly suppressed in soman-treated rats at almost all time points. Levels of adrenocorticotropin were similar in control and soman-treated rats. The results of this experiment demonstrate that a single exposure to soman may have long-lasting effects on neuroendocrine function.

Adrenocorticotropic Hormone↗
PubMed1988

Neuroendocrine correlates of sustained stress: the activity-stress paradigm.

Rats sacrificed after 4 days in the activity-stress paradigm or after 4 days of food restriction had significantly elevated levels of plasma corticosterone as compared to control rats. The approximately 5 fold increase in corticosterone in the stressed treatment groups was consistently found in all experiments. ACTH levels were elevated in activity-stress and food-restricted groups in some experiments but these increases were not statistically significant. Prolactin levels were significantly elevated in food-restricted group rats as compared to controls or activity-stress group animals in one experiment but this finding was not repeated in further experiments. In a second series of experiments, rats from activity-stressed and food-restricted treatment groups and controls were exposed to an acute stressor for 15 min prior to sacrifice to assess the effects of prior sustained stress on hormonal responses to an acute stressor. Exposure to 15 min of immobilization or intermittent footshock immediately prior to sacrifice increased plasma levels of corticosterone, ACTH and prolactin in control, food-restricted and activity-stressed rats. Generally, hormonal responses to the acute stress were similar in all treatment groups. However, in two experiments where the resting levels of corticosterone were especially elevated in the activity-stress group, the acute stress-induced rise in corticosterone was less than that seen for the other two treatment groups. In another experiment, administration of dexamethasone suppressed acute stress-evoked levels of ACTH and corticosterone in control, activity-stressed and food-restricted rats. Thus, rats exposed to 4 days of sustained stress were found to have consistently elevated resting levels of corticosterone.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1988

Chronic stress increases the binding of the A1 adenosine receptor agonist, [3H]cyclohexyladenosine, to rat hypothalamus.

We previously reported an increase in the binding of [3H]cyclohexyladenosine ([3H]CHA) to brain membranes from the hypothalamus of rats sacrificed following three days of chronic stress in an around-the-clock intermittent footshock avoidance/escape paradigm ("sustained performance" stress). Here we report stress-induced increases in [3H]CHA binding to hypothalamic membranes from rats stressed for 14 days in that escape/avoidance paradigm, in rats exposed to repeated restraint (3 hr/day for 10 days) and in rats exposed to four days of "activity-stress." Data from saturation binding experiments indicate that this up-regulation was due to an increase in the apparent number of [3H]CHA binding sites without change in affinity for [3H]CHA. Neither restraint for one three-hr period nor one 15-min exposure to intermittent footshock resulted in significant changes in [3H]CHA binding to hypothalamic membranes. Our present data demonstrate small but consistent increases in the number of [3H]CHA binding sites in hypothalamic membranes from rats stressed in several different chronic stress models but no change by acute stress.

Adenosine↗
PubMed1987

Effects of chronic stress on plasma corticosterone, ACTH and prolactin.

Rats were placed in a stressful environment for 24 hr per day and levels of plasma hormones were measured after varying numbers of days in the environment. Rats were habituated to operant chambers placed in sound-attenuated enclosures. Food pellets were available by lever press on a FR1 schedule. After 3 days of habituation, rats in the "stressed" group were trained to pull a ceiling chain to avoid or escape shock. Following training, stress trials, consisting of a consecutive sequence of 5 sec each of a warning light, warning tone and 0.16, 0.32, 0.65, 1.3 and 2.6 mA of footshock, occurred approximately once per 5 min around-the-clock. For the first day, the sequence was terminated when the ceiling chain was pulled. On subsequent days, 90% of all shock presentations could be avoided or escaped by chain pull; the remaining 10% of trials were inescapable and the entire sequence was presented. Control rats lived in identical chambers without presentation of shock. Rats were sacrificed after 1, 2, 3, 4, 7 or 14 days in this environment and levels of plasma corticosterone, ACTH and prolactin were determined. Levels of plasma corticosterone were elevated during the first 7 days in the stressful environment, but returned to control values by day 14. Levels of plasma ACTH and prolactin were similar in stressed and control rats at all time points measured. These data suggest that stress-induced changes in glucocorticoids but not in ACTH or prolactin might mediate some of the physiological changes that occur as the result of chronic stress.

Adrenocorticotropic Hormone↗
PubMed1987

Atropine sulfate increases pituitary responses to stress.

The effects of atropine sulfate pretreatment on pituitary indices of stress response were examined. Pituitary cyclic AMP and plasma prolactin increases following 15 min of acute stress were used as measures of stress response. Over a range of doses (0, 5, 10, 30 and 60 mg/kg), pretreatment with atropine sulfate increased the measured stress responses to footshock but had little or no effect on resting or non-stressed levels of the substances measured. The effects of atropine on response to immobilization were tested only at 5 mg/kg. At this dose, atropine sulfate, but not methylatropine nitrate, increased pituitary cyclic AMP response to immobilization stress demonstrating that the potentiation of the pituitary cyclic AMP stress response was not limited to footshock stress and suggesting that this effect of atropine was central rather than peripheral. Neither atropine nor methylatropine pretreatment at this dose potentiated prolactin response to immobilization stress.

Animals↗
PubMed1987

Effects of stress on [3H]cyclohexyladenosine binding to rat brain membranes.

The investigation of stress-induced changes in neuronal functioning is important to our understanding of mental disorders, stress-induced psychological impairment, and the emotional reactions of fear and anxiety. Data from previous animal studies have demonstrated various pituitary-adrenal responses to stress and also changes in brain neurotransmitters. We are investigating whether stress-induced neuroendocrine and brain monoamine changes are accompanied by concomitant changes in brain neurotransmitter and/or neuromodulator receptors. We have developed a behavioral paradigm of chronic stress which incorporates sustained stress, continuous performance, and disruption of sleep. Animals which are habituated to press a lever to receive food are trained in an active shock escape task. A matched set of animals housed in identical operant chambers but not exposed to footshock are used as comparative controls. [3H]Cyclohexyladenosine ([3H]CHA) (5-7 nM) binding to A1 adenosine receptors in hypothalamic membrane preparations from rats stressed for three days was fifteen percent higher than in matched controls. However, no differences in [3H]CHA binding were found in tissue preparations from frontal cortex, hippocampus, or striatum, when comparing stressed and matched control rats. Plasma corticosterone levels were higher in stressed rats than in matched controls.

Adenosine↗
PubMed1987

Paraventricular lesions abolish the stress-induced rise in pituitary cyclic adenosine monophosphate and attenuate the increases in plasma levels of proopiomelanocortin-derived peptides and prolactin.

Acute exposure to footshock stress increased the pituitary level of cyclic adenosine monophosphate (AMP) in vivo and sharply increased plasma levels of adrenocorticotropic hormone, beta-endorphin and beta-lipotrophic hormone, as well as prolactin. Seven days after bilateral lesions of the paraventricular nucleus of the hypothalamus, the pituitary cyclic AMP response to stress was totally eliminated and the increases in plasma levels of these pituitary hormones were blunted. We conclude that while the pituitary hormonal responses to stress might be mediated by several neurohumoral factors, the stress-induced increases in pituitary levels of cyclic AMP in vivo are mediated largely via corticotropin-releasing factor, released from neurons which project from the paraventricular nucleus to the median eminence.

Adrenocorticotropic Hormone↗
PubMed1986

Pituitary cyclic AMP and plasma hormone responses to epinephrine administration in vivo.

The present study was conducted to characterize the in vivo effects of epinephrine administration on levels of pituitary cyclic AMP and plasma hormones. Rats were injected with saline or epinephrine bitartrate (1 mg/kg lP) and sacrificed by decapitation 1, 5, 15, 30 or 60 min post-injection. Levels of pituitary cyclic AMP and plasma ACTH, beta-endorphin, beta-LPH, corticosterone and prolactin were determined by radioimmunoassays. The injection procedure itself was somewhat stressful as demonstrated by increased levels of plasma prolactin and ACTH 5 min following either saline or epinephrine injection. This "stress" response was rapid and short-lasting for the pituitary hormones. The response of the adrenal hormone, corticosterone, to saline injection was slower in onset and longer in duration. Pituitary cyclic AMP levels did not increase following saline injection. Epinephrine-injected animals displayed markedly elevated plasma levels of ACTH, beta-endorphin and beta-LPH at 15, 30 and 60 min as compared to control or saline-injected rats. In addition, levels of pituitary cyclic AMP were increased over 10 fold at these times. Levels of plasma prolactin, a stress-responsive hormone, were not significantly increased in epinephrine-injected animals as compared to saline-injected rats indicating that these later responses seem to be specific to epinephrine rather than to stress.

Adrenocorticotropic Hormone↗
PubMed1986

Diurnal variation in neuroendocrine response to stress in rats: plasma ACTH, beta-endorphin, beta-LPH, corticosterone, prolactin and pituitary cyclic AMP responses.

The effects of restraint stress applied at different times of the day on levels of five stress-responsive plasma hormones (ACTH, beta-endorphin, beta-LPH, corticosterone and prolactin) and pituitary cyclic AMP levels were assessed. Different groups of rats were subjected to 15 min of restraint stress at 2-hour intervals over a 24-hour period. Rats were sacrificed immediately upon removal from their home cage (controls) or immediately following restraint (stressed). The time of day of stress exposure markedly affected the stress responses measured. Generally, responses to stress applied at the beginning of the dark cycle (18:00) were less than those seen following stress applied at the beginning of the light cycle (06:00). Stress at 06:00 increased levels of pituitary cyclic AMP 10-fold, while stress applied at 18:00 did not significantly increase pituitary cyclic AMP levels. In stressed rats, high correlations were seen among levels of hormones derived from the common precursor, proopiomelanocortin (ACTH, beta-endorphin, beta-LPH) and between these hormones and levels of pituitary cyclic AMP. These findings support the hypothesis that pituitary cyclic AMP is involved in the stress-induced release or synthesis of the pituitary hormones ACTH, beta-endorphin, and beta-LPH.

Adrenocorticotropic Hormone↗