Biomedical subjects

R L Isaacson

Publications and source records attributed to R L Isaacson.

At least 55 records · Page 3Linked to original sources

PubMed1986

The effects of verapamil and ethanol on body temperature and motor coordination.

Male, adult mice of the Binghamton heterogeneous stock received one of two doses of ethanol (1.0 g/kg or 2.0 g/kg in saline) alone or in combination with the calcium (Ca2+) slow channel blocker, verapamil (5.45 mg/kg in 25% v/v ethanol in saline). Hypothermic responses and motor incoordination were assessed in terms of rectal temperatures and rotorod activity both 20 and 60 min after drug administration. Verapamil alone did not affect body temperature, but it potentiated ethanol-induced hypothermia at both post-administration test times. Both verapamil and ethanol impaired muscular coordination and these effects were additive at the two observation periods. Verapamil did not affect ethanol blood levels from 10 to 80 min after administration of the drugs. Since motor impairment was observed when verapamil was administered with only its ethanol vehicle, this suggests a powerful interactive effect between the two drugs.

Animals↗

PubMed1986

Character of (D-Phe-7) ACTH4-10-induced excessive grooming.

Rats receiving (D-Phe-7) ACTH4-10 exhibited excessive grooming during the first half of the hour-long observation period. This resulted in total grooming scores of about one-half of those produced by the longer ACTH fragments, ACTH1-24 or ACTH1-16 NH2. The excessive grooming induced by (D-Phe-7) ACTH4-10 was due to an enhancement of duration of grooming bouts and not to an increase in the frequency of occurrence. Furthermore, the neuropeptide-induced excessive grooming was eliminated by prior treatment with naloxone.

Adrenocorticotropic Hormone↗

PubMed1986

Melanocortins, neural plasticity and aging.

Peptides derived from ACHT and alpha-MSH are known to exert trophic influences on peripheral and central nervous structures. Age-related brain diseases may in part be related to loss of neural plasticity. Melanocortins improve adaptional abilities of the nervous system. Chronic treatment with melanocortins may counteract age-related brain pathology.

Adrenocorticotropic Hormone↗

PubMed1985

Nimodipine's interactions with other drugs: II. Diazepam.

Adult Binghamton Heterogeneous (HET) stock mice were administered one of three doses of diazepam (0.1, 2.5, or 5.0 mg/kg) immediately followed by a second injection of either the slow calcium channel blocker, nimodipine (Bay e 9736), or its vehicle. Hypothermic responses and muscular incoordination were measured twenty and sixty minutes later as assessed by changes in rectal temperature and motoric activity on a rotating rod. Nimodipine (5 mg/kg) alone did not significantly affect body temperature or motor coordination. However, when administered in combination with the two highest doses of diazepam, nimodipine significantly potentiated the hypothermic response produced by these doses both twenty minutes and sixty minutes post-injection. Administration of high doses of diazepam (2.5 and 5.0 mg/kg) resulted in significant motor incoordination at both observation periods, but this effect was not potentiated by nimodipine.

Animals↗

PubMed1985

Nimodipine's interactions with other drugs: I. Ethanol.

Adult mice (Binghamton Heterogeneous stock) received different doses of ethanol (0.5, 1.0, or 2.0 g/kg) administered alone or in combination with the voltage-sensitive calcium channel antagonist, nimodipine (Bay e 9736). Both 20 and 60 minutes later, sensitivity to ethanol was assessed in terms of rotorod activity and changes in rectal temperatures. Nimodipine (5 mg/kg) alone did not alter rectal temperature or motor coordination, but at both observation periods nimodipine potentiated the hypothermia induced by the highest dose of alcohol (2.0 g/kg) and exaggerated alcohol-induced motor incoordination at all doses. The present set of results indicates that the inhibition of voltage-dependent calcium channels can exaggerate ethanol-induced effects.

Animals↗

PubMed1985

The effects of Org 2766 on the performance of sham, neocortical, and hippocampal-lesioned rats in a food search task.

The behavioral effects of an ACTH4-9 variant, Org 2766, given for one week postoperatively at a dose of 1 microgram/rat daily, were evaluated in animals given hippocampal, neocortical, or "sham" lesions. After the week during which the injections were given, the animals were tested for 5 days in a food-search task in which food was hidden in two recessed holes in the floor. On the next day the ability of the rats to find food in these same two baited holes was tested in the presence of 14 additional holes that were not baited. On the following day, the animals were tested again, this time with all 16 holes baited. To assess the long-term effects of Org 2766 treatment, the animals were tested once again 2-3 months later in the same apparatus with 16 empty holes. In general, rats with lesions restricted to the neocortex were severely impaired in the task and were unaffected by prior treatment with Org 2766. Animals with hippocampal damage quickly learned the task and were hyperactive. During the test session with 16 baited holes they showed differential behavioral changes suggesting attentional deficits not seen in "sham" operated rats. These deficits were attenuated by prior Org 2766 treatment, whereas the lesion-induced hyperactivity was not. Treatment with Org 2766 impaired all aspects of performance of "sham" operated animals.

Adrenocorticotropic Hormone↗

PubMed1985

Ethanol-induced grooming in mice selectively bred for differential sensitivity to ethanol.

In rats, excessive grooming follows the application of several forms of stress. The injection of alcohol may be considered as a stressor, since it increases plasma corticosterone levels. The present study examines the effects of ethanol injections on grooming in two lines of mice selected for differences in their hypnotic response to ethanol, i.e., the long sleep (LS) and short sleep (SS) lines developed at the Institute for Behavior Genetics at the University of Colorado at Boulder. Various subhypnotic doses of ethanol produced excessive grooming in the SS line, but this did not occur in the LS line. The SS mice also displayed more "novelty-induced" grooming compared to the LS mice after repeated exposure to the testing situation. The increase in excessive grooming in both the ethanol-induced and the novelty-induced excessive grooming situations was most apparent in the second half of the observation period.

Animals↗

PubMed1985

Suppression of corticosterone synthesis alters the behavior of hippocampally lesioned rats.

The suppression of corticosterone synthesis with metyrapone (25 mg/kg) reduced the hyperactivity and altered the exploratory activity of hippocampally lesioned animals (HPC) in the open field to the level of cortical and sham controls (Experiment 1). In a second experiment, corticosterone (600 micrograms/kg) pretreatment 2 h, but not 1 h, before metyrapone partially restored the hyperactivity of HPC animals that had been decreased by the corticosteroid-suppressant drug. Alterations in exploratory behavior induced by metyrapone were also prevented by corticosterone pretreatment. The results suggest that the suppression of corticosterone in hippocampally lesioned animals produces a normalization of behavior that can be prevented by pretreatment with corticosterone.

Animals↗

PubMed1985

ACTH4-10 produces a transient decrease in septal hyperemotionality.

The administration of doses of ACTH4-10 that have been shown to be effective in producing enhanced peripheral nerve regeneration did not produce the enhanced rate of decline in hyperemotionality produced by administration of the ACTH4-9 variant Org 2766. Long-term changes in septal reactions in training situations were likewise not affected by ACTH4-10. These results indicate that, despite similar peripheral nerve growth effects, these two ACTH-related agents (ACTH4-10 and Org 2766) produce quite different long- and short-term effects on rats with septal area damage.

Adrenocorticotropic Hormone↗

PubMed1984

Differentiation of basal ganglia dopaminergic involvement in behavior after hippocampectomy.

Large bilateral aspiration lesions of the hippocampus in rats lead to a variety of changes in spontaneous behavior measured in an open field/hole board, relative to sham and neocortically lesioned controls. These changes include increased locomotion, and decreased grooming frequency and rearing bout duration. When animals were injected with the dopamine (DA) agonist 3,4-dihydroxyphenylamino-2-imidazoline (DPI: 0.5, 1.0 and 5.0 microgram) into the nucleus accumbens one week after surgery, the behavior of hippocampally lesioned rats was restored to levels not different from control lesioned rats. Haloperidol injections (0.05, 0.1 and 0.5 microgram) into the caudate nucleus were not able to do this. Further, DPI injected into the caudate month after surgery was also able to attenuate some of the effects of hippocampal damage. On the other hand, haloperidol injections into the nucleus accumbens did not influence behavior. The results are interpreted in terms of hippocampal lesion-induced alteration of a balance in basal ganglia DA systems, indicated by modified response to pharmacological intervention and which mediate the behavioral effects of the lesion.

Animals↗

PubMed1984

Classical contingencies in rats with hippocampal lesions.

Hippocampal, cortical and sham lesioned rats were trained to discriminate between two odors, in non-contingent, partially contingent, and perfectly contingent schedules. In the non-contingent situation both odors signaled shock with probability of 0.5. In the partially contingent situation one odor signaled shock with probability of 0.5 and the other "no shock" with probability of 1. In the perfectly contingent situation one odor signaled shock and the other "no shock" with probabilities of 1. In the non-contingent schedule none of the three surgical groups evidenced learning, in the partially and perfectly contingent cases the hippocampally lesioned animals performed so as to indicate greater learning of the aversion than did the cortically lesioned or the sham operated animals. It is suggested that the behavior of animals with hippocampal lesions is more sensitive to contingencies than that of normal animals.

Animals↗

PubMed1984

Hippocampal damage: effects on dopaminergic systems of the basal ganglia.

Although the research topics discussed in this chapter cover a substantial range of areas, methods, and behaviors, there is a consistent central issue: the alterations of brain and behavior subsequent to hippocampal lesions. The initial hypothesis that important secondary changes occur in the basal ganglia after hippocampal lesions has been sustained, at least in part, but other and unexpected results have been obtained that both clarify and mystify at the same time. The restoration of normal locomotion to animals with hippocampal damage by the application of a DAi agonist, DPI, to n. accumbens certainly supports our general idea, but the fact that membrane and transmitter changes in accumbens are transitory needs to be explained and perhaps related to alterations in DA receptor populations. The fact that intra-accumbens DPI can restore ACTH-induced excessive grooming at 28 days after hippocampal damage supports the idea that progressive changes are occurring in DA receptors in n. accumbens, but we need to know their nature more precisely. To do this, however, will probably require advances in our general knowledge of central DA receptors. One of the more interesting aspects of our observations is that the intra-accumbens administration of DPI restores normal behavioral patterns in several types of behaviors, especially locomotion and the excessive grooming response. These two behaviors are not closely linked in nature because large changes can occur in them independently, given appropriate conditions for testing. On the basis of available evidence both of these behaviors seem linked to activities in forebrain DA systems. This would further support the idea that the hippocampus modulates DA activities in basal ganglia systems. The results that suggest the presence of multiple sites for the central induction of grooming were also unexpected. As evidence mounts in support of this idea, it is likely that the one located in n. accumbens is more influenced by hippocampal destruction than the region(s) affected by icv neuropeptide administration. The interactions that take place in the basal ganglia can be extensive. Afferents from the entirety of the neocortical surface, the limbic system, and the projections from the brainstem DA cell groups meet in the striatum and ventral striatum. The efferents from this region not only reach motor cortical and subcortical sites but also project back onto diffusely projecting monoaminergic cells of the brainstem.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenocorticotropic Hormone↗

PubMed1984

Adrenergic nervous system alteration and ethanol-induced narcosis in long-sleep and short-sleep mice.

Long-sleep (LS) and short-sleep (SS) mice were pretreated with either propranolol or phentolamine, followed by a hypnotic dose of ethanol. Pretreatment with propranolol, but not phentolamine, significantly reduced ethanol sleep time in LS mice. The SS mice were not affected. In a second study propranolol pretreatment was given subsequent to ethanol at various doses, different for each line, that produced similar sleep time durations in both lines. Under these conditions, propranolol decreased sleep time in both LS and SS mice. These data lend support to the idea that noradrenergic mechanisms play a role in the mediation of the hypnotic effects of ethanol.

Adrenergic Fibers↗

PubMed1983

Dopamine depletion in nucleus accumbens reduces ACTH1-24-induced excessive grooming.

Animals were pretreated with 6-OHDA or ascorbate vehicle injected into the nucleus accumbens and tested 10 days later for excessive grooming induced by intracerebroventricular injection of ACTH1-24. The animals pretreated with 6-OHDA showed a significant decrease in excessive grooming produced by the neuropeptide and this reduction was seen only in the last 30 minutes of a 60-min test session. The results suggest an interaction of ACTH with dopamine systems on the onset and maintenance of excessive grooming.

Adrenocorticotropic Hormone↗

PubMed1983

The time course of excessive grooming after neuropeptide administration.

In this paper we review the temporal pattern of excessive grooming in the hour or so following the central injection of ACTH1-24 in the rat. Changes in the grooming pattern after specific neuropharmacological manipulations of dopaminergic and opiate-related systems are presented which indicate a differential sensitivity of the grooming responses at different times after injection. The grooming affected by dopaminergic antagonists and opiate agonists and antagonists occurs in the last 30 min of the observation period while that found earlier is unaffected. It is also the grooming in this last 30 min of the observation period term tolerance to central administration of ACTH1-24. In contrast lesions of the central nervous system that affect excessive grooming, i.e., the substantia nigra and the hippocampus, reduce grooming throughout the observation period. The present analysis has provided evidence for dopamine/opiate insensitive and sensitive systems in excessive grooming, and thus temporal aspects are of extreme importance to the understanding of central neuropeptide influences on behavior.

Adrenocorticotropic Hormone↗

PubMed1983

Changes in open-field behaviors following septal lesions in rats.

Sixteen rats were tested for 10 min in an open field on postoperative Days 6--7, 11--12, 19--20, and 38--39, under two conditions of illumination. Septal lesions produced alterations in activity, rearing, and grooming that changed over the repeated tests. Septal rats initially had low activity scores that increased over testing to a level higher than that of controls, low rearing behavior that increased over sessions but always remained below control levels, and low grooming scores that became equivalent to controls by postoperative Days 38--39. These findings indicated that repeated testing given only postoperatively in an open field resulted in hyperactivity, decreased rearing, but no differential effect in grooming. The time course of change in these three behaviors was not identical.

Animals↗

PubMed1983

An ACTH4-9 analog (ORG 2766) speeds recovery from septal hyperemotionality in the rat.

The amount of hyperemotionality initially demonstrated after septal area lesions was reduced, and the rate at which the hyperemotionality attenuated over repeated testing, was enhanced by the administration of an ACTH4-9 analog, ORG 2766. This ACTH fragment was given for 4 consecutive days after surgery but terminated before testing began. Two weeks after the daily tests of emotionality, the animals were trained in a two-way active avoidance task. The typical increase in avoidance behavior seen in animals with septal lesions was observed in the lesioned animals tested with ORG 2766, but the usual high number of intertrial responses was greatly reduced in these animals. The results indicate that even after a brief series of ORG 2766 administration, there are changes in emotionality that may last for an extended period of time after the cessation of treatment.

Adrenocorticotropic Hormone↗

PubMed1982

Catecholamine alterations in basal ganglia after hippocampal lesions.

Rats were given sham, cortical, or hippocampal lesions and sacrificed 7 or 28 days following surgery. Levels of norepinephrine, dopamine, and the major dopamine metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid (HVA), were assayed in 3 brain regions. At day 7 there was a decrease in dopamine utilization and a decrease in norepinephrine levels in the nucleus accumbens after hippocampal damage but both of these measures returned to normal levels by day 28. In the neostriatum HVA levels decreased at day 7 after hippocampal damage. The utilization of dopamine in the neostriatum was decreased at day 28 in animals that received neocortical lesions but this was not observed in animals with hippocampal destruction. No effects of any lesion at any day were found in the olfactory tubercle region, the third brain region analyzed. It is thought that the removal of hippocampal and neocortical input to the basal ganglia influences catecholamine function reflected in the loss and subsequent recovery of dopamine utilization.

3,4-Dihydroxyphenylacetic Acid↗