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Biomedical subjects

R L Isaacson

Publications and source records attributed to R L Isaacson.

At least 37 records · Page 2Linked to original sources
PubMed1990

Actions and interactions of calcium modulators and ethanol on rat atrial membrane potentials.

The effects of ethanol and dihydropyridines on atrial membrane potentials (MP) were studied. Rat atrial strips superfused with Tyrode's solution (36 degrees C) were driven at 5 Hz while recording MP with intracellular microelectrodes. Bay K 8644 7 X 10(-7) M (BAYK) increased the amplitude of the action potential (AAP) without affecting the resting membrane potential (RMP) or the Vmax of phase 0 (Vmax 0). The velocity of change in voltage decreased at the beginning of the repolarization, causing an increase in the action potential duration (APD), but it was not modified at negative voltages. Nimodipine 4.2 X 10(-6) M reduced the AAP without affecting RMP or Vmax 0. The velocity of change in voltage increased at the beginning of the repolarization, causing a decrease in the APD, but was not modified at negative voltages. Ethanol 5.3 X 10(-2) M exerted actions similar to those of nimodipine. Simultaneous exposure to ethanol and nimodipine resulted in changes not different from those obtained with each of the two compounds. The MP remained unchanged when the preparations were exposed to ethanol and BAYK simultaneously. In summary, ethanol and nimodipine exerted similar actions on the atrial MP while BAYK had opposite actions. The effects of ethanol and BAYK cancelled each other.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1990

Inotropic effects of ethanol and dihydropyridines on the guinea pig heart atrial muscle.

The effects of ethanol and/or dihydropyridines (DHPs) on force of contraction of atrial muscle were studied. Guinea pig atrial strips superfused with Tyrode's solution (36 degrees C) were driven (1.5 Hz) while recording muscle tension. Bay K 8644 (BAYK) increased, while nimodipine or ethanol reduced, the peak tension developed and the maximum velocity of development of tension. The effects of ethanol were readily reversible, but those of the DHPs were not. The combined actions of ethanol and DHPs were the result of the synergism or antagonism of the drugs tested. The shorter duration of the action of ethanol resulted in the effect of DHPs being still evident well after the exposure to the drugs ended. In summary, ethanol and nimodipine exerted depressant actions on atrial contractile force, while BAYK had opposite effects. The different mechanisms of action may explain the different duration of the effects of ethanol (physical agent) and DHPs (receptor-binding chemicals).

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1990

Pretreatment effects on nitrite-induced methemoglobinemia: saline and calcium channel antagonists.

This study was undertaken to evaluate the effects of pretreatment with calcium channel antagonists (nimodipine or verapamil) on the formation of methemoglobin produced by sodium nitrite. Unexpectedly, the pretreatment of animals with control injections of physiological saline 2 hours before the nitrite administration reduced the amount of methemoglobin found in the blood 25 minutes later. When either of the calcium channel antagonists was given 2 hours before the administration of sodium nitrite, the saline effect was eliminated. When the injections of physiological saline or either of the calcium channel blockers were divided 24 hours before the nitrite administration, all reduced the amount of methemoglobin formed relative to rats that received no pretreatment. A tentative hypothesis is that the reduction of the nitrite-induced methemoglobin can be induced by the stress of handling and intraperitoneal injection and that this stress effect can last at least 24 hours. It is likely that whatever stress-related mechanism is involved in reducing methemoglobin levels, this effect can be reduced by the presence of "L channel" voltage-sensitive calcium antagonists or their active metabolites.

Animals↗
PubMed1990

The residual spatial abilities of hippocampally lesioned rats can be enhanced by peripheral sympathetic-adrenal interventions.

In order to test the possible effectiveness of peripheral interventions with the adrenergic system for the alleviation of certain disorders that typically follow bilateral hippocampal lesions, rats with bilateral lesions of the hippocampus, the overlying neocortex, or sham operations were tested at two postoperative times in the Morris water maze, a frequently used "spatial task." Half of the animals in all groups were exposed to the adrenergic manipulations, i.e., a chronic, 7-day, systemic bretylium regime (5 mg/kg) and, in addition, a peripheral injection of norepinephrine (4 micrograms/kg) 30 min before the start of each training day. The other half received saline chronically and a single saline injection before each training day. Five days of training were given at each of the two training periods. The first began 7 days after surgery while the second began 33 days after surgery. As expected, the hippocampally lesioned animals were severely impaired in the task. The adrenergic treatment produced enhanced performances in the rats with hippocampal lesions at both training sessions, although the improvement was greatest at the later period. Although the animals receiving the pharmacologic treatment located the general area of the hidden platform better than the saline-treated animals with hippocampal lesions, the treated animals were still impaired, swimming directly to the hidden platform on fewer trials than did animals in the other groups.

Adrenal Glands↗
PubMed1990

Nimodipine accelerates recovery from the hyperemotionality produced by septal lesions.

Rats with large electrolytic lesions of the septal area were given the calcium channel antagonist nimodipine (70 micrograms/kg, ip) or its vehicle on the day of surgery and for 3 subsequent days. They were tested for emotionality and compared to control rats for 10 days beginning on the third day after surgery. Forty days after surgery all animals were trained in a two-way active avoidance task for 120 trials. Nimodipine reduced the hyperemotionality found after septal lesions as early as the first test day, and increased the rate of recovery toward control levels on subsequent days. Both septal-lesion groups exhibited more avoidance responses than controls, even though the intertrial crossings were enhanced only in rats with septal lesions that did not receive nimodipine.

Animals↗
PubMed1990

Brain plasticity after damage.

This is a brief summary of our research on the prevention or reduction of the effects of brain damage. I believe that the results contain a number of exciting promises. At this time, the greatest hope for effective remedial interventions comes from the choline and metyrapone studies. However, I am also reminded of the components a psychiatrist who worked with children in the heart of Philadelphia made some 20 years ago at a conference on mental retardation. He said that the most significant contribution to the elimination of mental retardation in his city would be the elimination of lead-based paints from the walls of ghetto apartments, an intervention second only in effectiveness to the elimination of the ghettos themselves. The importance of early interventions with individuals suffering brain damage, either general or specific, is clearly recognized. In research now well underway, Yong Shen, William Smotherman, and I have found encouraging results indicating that both short- and long-term effects of hypoxia induced by clamping the rat's umbilical cord can be attenuated by the prior administration of a calcium L channel antagonist. If those results are upheld in further studies, the principles of prevention of damage described in this article for the adult may prove to be even more potent in the young.

Animals↗
PubMed1989

Brief ganglioside treatment produces delayed enhancement of functional recovery after medial septal lesions.

The effects of a 5-day ganglioside (GM1) treatment (30 mg/kg) on body weight and water intake subsequent to medial septal lesions were evaluated for 44 consecutive days. In addition, activity, rearing, and repetitive motor acts were measured on postsurgery days 5, 10, 40, and 60. The rate of increase in the body weights of rats with medial septal lesions treated with GM1 was equivalent to that of controls, while untreated rats with such lesions had reduced body weights. Rats with medial septal lesions treated with GM1 also exhibited movement times and frequency of repetitious motor acts similar to those of control rats by postsurgery day 60. No differences were found in water intake between any of the groups. Rats with medial septal lesions, whether treated with GM1 or not, had equivalent frequencies of rearings that were lower than control rats. This study emphasizes that even brief regimes of GM1 administration can exert behavioral changes in brain-damaged rats well after the treatment was administered, i.e. 40-60 days after surgery.

Animals↗
PubMed1989

Actions and interactions of dihydropyridines and ethanol on the rat sinus node.

The actions and interactions of dihydropyridines (DHPs) and ethanol on sinus node (SN) automaticity were studied using rat sinoatrial preparations superfused with Tyrode's solution at 37 degrees C. Intracellular microelectrodes were used to monitor SN rate (SNR). The automaticity of the SN was not affected by nimodipine 10(-10) M, but it was depressed by a higher concentration of this calcium antagonist (10(-8) M). The racemic compound (+/-)Bay K 8644 had a dose-dependent biphasic chronotropic action: At 10(-8) M it decreased the SNR, while at 10(-7) M it increased the SNR. The negative component was blocked by atropine. A small concentration of ethanol (1.8 x 10(-2) M) had a positive chronotropic effect on the SN, and this action was blocked by nimodipine 10(-10) M. This small concentration of ethanol did not modify the chronotropic effects of either of the DHPs. A higher concentration of ethanol (5.3 x 10(-2) M) did not by itself affect the SNR, but it antagonized the chronotropic actions of the two DHPs.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1989

Posttraining or pretest administration of nimodipine fails to affect retention of a simple learned association.

In previous experiments, the antagonist of voltage-sensitive calcium channels, nimodipine, given before training, enhanced the retention of an acquired preference for white-left relative to black-right in a two compartment apparatus. In the present experiments we attempted to determine if the retention effects produced by the drug could be attributed to effects occurring in the posttraining period. Various groups of rats received posttraining injections of nimodipine or its vehicle and two hours prior to testing received a second injection of nimodipine or its vehicle or no injection at all. All rats were tested for retention of the association twice, both 24 and 48 hr after acquisition. No posttraining or pretesting drug effects were found. This would support the view that the enhanced retention found after treatment with nimodipine found by ourselves and by others is due to a change in the animals at the time of acquisition.

Animals↗
PubMed1989

The effects of unilateral destruction of fimbria-fornix and supracallosal pathways in the rat.

Rats with unilateral lesions of either the supracallosal regions (including the dorsal cingulate cortex) and the fimbria-fornix either on the same (S) or the opposite (O) sides of the brain were studied in a 16-hole open field without pharmacologic intervention and, subsequently, after 0.1 and after 1.0 mg/kg scopolamine HBr. Their performances were compared with those of unoperated control animals subjected to the same testing regime. Certain of their behaviors were compared with those of a larger number of animals with bilateral hippocampal destruction (and their control groups) from prior studies. Unilateral lesions of fimbria-fornix and supracallosal afferents to the hippocampal formation produced a decrease in hole poking activity relative to control animals. A further decrease in hole-poking behavior, coupled with increased locomotion, was observed in rats with fimbria-fornix and cingulate cortex lesions on opposite sides of the brain (group O). The smaller dose of scopolamine accentuated these effects. Indeed, the behavior of group O after scopolamine treatment was similar to animals with large bilateral hippocampal lesions. The large dose of scopolamine induced stereotyped rearing or hole poking in the brain-damaged animals but not in the control group. These findings suggest that both the fimbria-fornix and the supracallosal pathway is necessary for normal hippocampal function and that the behavioral deficit is greater when these structures are damaged on the opposite sides of the brain.

Afferent Pathways↗
PubMed1988

Spontaneous bodily rotations and direction of locomotion at different times after radio frequency lesions at sites in and near the substantia nigra.

Rats were prepared with radio frequency lesions of the dorsolateral or ventromedial regions of the substantia nigra. Other rats were prepared as operated and unoperated controls for each type of lesion. Their behavior was evaluated in an open field at postoperative days 2, 7, 10, and 15. Three types of behavioral changes were observed over time: those noticeable for a brief period, i.e., a few days, after the lesion (rotational behavior), those lasting 7-10 days after the lesion (turning preferences) and those lasting through the end of the experiment that may be permanent (enhanced locomotion). The early effect of the medioventral lesions was pronounced contralateral rotation while the early effect of the dorsolateral lesion was ipsilateral rotation. This effect of the dorsal lateral lesions was reversed on test days 7 and 10. Lesion-induced turning changes associated with forward locomotion were observed on these two test days as well. By 15 days after surgery the only demonstrable effect of either lesion was enhanced locomotion. The results are discussed in terms of various theories of substantia nigra regulation of motor activities.

Animals↗
PubMed1988

The effect of a calcium antagonist on the retention of simple associational learning.

Using a newly developed training paradigm, rats were trained to associate a spatial location and a black interior with mild footshock and another adjacent location with white interior with the absence of footshock in three independent experiments. Retention of these associations was measured 24 and 48 hr after training in situation in which the animals could move freely between the black and white locations over a 90 sec test. Other rats were subjected to a control procedure in which shock was received on both the black and the white sides of the apparatus. In each of the experiments, half of the animals in the experimental and the control groups were trained following the administration of the calcium slow channel blocking agent, nimodipine (5 mg/kg), and the other half after saline administration. In experiment 1, the injections were given 15 min before training. In experiment 2, the injections were given chronically, over a 6 day period before training. In experiment 3, the animals were given a single injection 7 days before training. In all cases, retention was examined both 24 and 48 hr after training. The results were that the experimental procedures produce a strong aversion to the black portion of the apparatus. The greatest amount of retention was found in animals that had received the chronic injections, whether they were of saline or of nimodipine. In every aspect of retention in which the saline-treated rats were less than perfect in retention, the nimodipine animals exhibited superior performance.

Animals↗
PubMed1988

Changes in the distribution of the neuron-specific B-50, neurofilament protein and glial fibrillary acidic proteins following an unilateral mesencephalic lesion in the rat.

Following a unilateral electrolytic lesion in the ventral rat mesencephalon, changes in the immunocytochemical distribution of the neuron-specific B-50, neurofilament (NF) protein and glial fibrillary acidic (GFAP) proteins were studied around the lesion after 0, 3, 10 and 28 days. At all recovery times, the controls displayed on immunostaining with anti-B-50 and anti-neurofilament antibodies, a characteristic pattern of synaptic and neuritic localization of these antigens, whereas anti-GFAP staining revealed a distribution typical for astrocytes. The lesion was characterized by a center of coagulated material that exhibited immunoreactivity to B-50 (BIR) and NF (NFIR), but never GFAP-immunoreactivity. From 3 days on, the center became surrounded by disintegrating cells which were unreactive to the antibodies. The antigen distribution changed temporally, predominantly at the lesion rim. By 10 and 28 days postlesion, additional BIR was observed as punctuate dots in fibers and membranes of neurons. Enhanced NFIR was detected in fibers and cell bodies. Many astrocytes were detected around the lesion rim, forming by 28 days postsurgery a barrier between the lesion cavity and the uninjured tissue. Our study shows that distribution changes in B-50, NF and GFAP around the lesion may indicate local degenerative and adaptative processes as a temporal response to brain trauma.

Animals↗
PubMed1988

Excessive grooming induced by the administration of codeine and morphine.

Previous studies have shown that peripheral injections of the codeinone RX 336-M can induce excessive grooming in rats in an age-dependent fashion. The present experiment demonstrates that codeine, itself, also induces excessive grooming but with apparent equal effectiveness at all ages tested. Because of the structural similarity between codeine and morphine, the effects of intraperitoneally administered morphine were examined as well. Morphine was found to produce a temporal course of excessive grooming quite different from that produced by codeine. Morphine did not affect grooming in the first half (30 min) of the observation period, but accentuated it, briefly, for the next 30-45 min. Intraventricular administration of codeine at doses of 0.3 or 1.0 microgram/3 microliter had no effect on grooming in animals previously shown to demonstrate excessive grooming in response to either dose.

Aging↗
PubMed1987

CCK-8 elicits grooming: cross tolerance to ACTH1-24.

Rats received lateral intracerebroventricular (icv) injection of sulfated or desulfated cholecystokinin octapeptide (CCK-8-S or CCK-8-D, respectively) and subsequent grooming behaviors were observed using a behavioral sampling technique. CCK-8-S (2.0 to 4.0 micrograms in 10 microliter) elicited a significant increase in grooming behaviors relative to the controls, but the relatively inactive CCK-8-D did not. Excessive grooming induced by CCK-8-S produced less grooming than did the adrenocorticotropic hormone fragment, ACTH1-24 (1.0 microgram in 10 microliter). An icv injection of CCK-8-S 3 h before the icv injection of ACTH1-24 inhibited the usual excessive grooming produced by the ACTH. Conversely, prior injection of ACTH1-24 abolished the increased grooming induced by CCK-8-S. Thus, the sulfated cholecystokinin octapeptide and ACTH1-24 exhibited short-term cross tolerance for excessive grooming. These results suggest that the colocalization of corticotropin releasing hormone and CCK-8 in neurons may have functional significance in connection with stress-related neuronal systems.

Adrenocorticotropic Hormone↗
PubMed1987

Age- and sex-related induction of excessive grooming and "wet-dog" shakes by the codeinone RX 336-M in the rat.

Peripheral administration of the dihydrocodeinone RX 336-M (6 mg/kg) stimulated vigorous "wet-dog" shakes and excessive grooming in young drug-naive rats. The effects of RX 336-M were greater in younger than in older animals of both sexes, and were greater in 39-day-old male rats than in female rats of the same age. In a second experiment, female rats were pretreated with testosterone benzoate (1 mg/kg/day) for 1 week prior to testing the effects of RX 336-M at 39 days of age. The sex hormone pretreatment enhanced the ability to RX 336-M to induce "wet-dog" shakes and excessive grooming in female rats. The results suggest that both sex- and hormone-dependent developmental status are critical in the display of the so-called "quasi-morphine withdrawal syndrome." The results imply, and are consistent with previous studies which suggest, that different neural mechanisms underlie the behavioral responses induced by ACTH and RX 336-M.

Age Factors↗
PubMed1987

The GM1 ganglioside hastens the reduction of hyperemotionality after septal lesions.

The purpose of the present study was to assess the effects of ganglioside treatment on changes in emotional, activity, and avoidance behaviors following septal brain damage. Rats were treated with GM1-gangliosides either before and after septal lesions, or only after septal lesions and tested for emotionality on 10 consecutive days beginning on the second day after surgery. The ganglioside treatment decreased the emotionality of rats with septal damage on the first test day, and enhanced their rate of recovery to control levels of emotionality. Septal rats treated with gangliosides had activity, rearing, and avoidance behaviors equivalent to nontreated septal rats; however, lesioned rats treated with GM1 showed reduced intertrial crossings during avoidance conditioning. These results suggest that the changes in emotional behavior of septal rats treated with GM1 occur shortly after the lesion.

Animals↗