Biomedical subjects

R F Berman

Publications and source records attributed to R F Berman.

69 records · Page 4Linked to original sources

PubMedDate not supplied

Reduction of amygdaloid kindled seizures by an analog of ACTH/MSH.

A behaviorally potent analog of ACTH/MSH(4-9), ORG-2766, markedly reduces both physiologic and behavioral components of convulsive seizures in an animal model of epilepsy--the amygdaloid kindled rat. We believe that such non-endocrine analogs of ACTH/MSH fragments may be clinically useful anticonvulsants, particularly in chronic applications, provided that their permeation of the blood-brain barrier can be improved.

Adrenocorticotropic Hormone↗

PubMedDate not supplied

Correlation of behavioral and cerebrovascular functions in the aging rat.

Regional cerebral blood flow (rCBF), maze performance and the influence of environmental enrichment on these parameters were studied in Sprague-Dawley rats aged 6, 12 and 24 months. Learning ability in a complex sequential T-maze (Stone maze) progressively declined with increasing age in rats which were normally housed in standard caging. Environmental enrichment significantly improved maze performance but did not prevent the age-dependent impairment. Following completion of the learning studies, rCBF was measured in each of 13 brain regions in conscious, unrestrained, resting animals. In the absence of any significant change in cardiac output over the entire age range, rCBF was lower in all brain regions by an average of 16% in 12-14 month old rats and 8% in aged rats (24-26 months old); the occipital cortex, inferior and superior colliculi and hypothalamus were particularly affected regions in both age groups. The sharp reduction of rCBF that occurred between 6 and 12 months of age did not reflect, and probably preceded the progressive decline in maze performance. Such highly significant age-related changes in rCBF were not affected, however, by environmental enrichment procedures. This contrasts with the substantial influence of enrichment on maze performance. Finally, mean brain blood flow and mean cortical blood flow correlated inversely and significantly with average daily numbers of errors made by 24 month old rats during Stone maze acquisition.

Aging↗

PubMedDate not supplied

Cerebrovascular permeability and cognition in the aging rat.

Regional cerebrovascular permeability-capillary surface area products (rPS) and brain vascular space (BVS) were measured in aging, conscious, unrestrained Sprague-Dawley rats. Three groups of animals were examined: young-mature (6 months), middle-aged (12-14 months), and old (24-26 months) rats. Complex maze learning had been previously characterized in these same animals. Maze learning declined with age. Brain vascular space did not differ significantly with age in any brain region. However, small, but significant age-dependent decreases in rPS (25-33%) were observed. These decreases occurred mainly in the old animals in the basal ganglia and parietal cortex, and in the middle-aged and old rats in the olfactory bulbs. Significant and unexpected positive average correlations between brain permeability-capillary surface area products (PS) and learning errors occurred primarily in young rats and were attributable mainly to changes in 5 of 14 brain regions; hypothalamus, hippocampus, parietal cortex, septal area and superior colliculus. The higher correlations between maze learning errors and PS in young animals may indicate dynamic regulation of this cerebrovascular parameter which is lessened with aging. Average correlations between PS and cerebral blood flow also were determined and found to be generally small and not significant for most brain regions and age groups.

Aging↗

PubMedDate not supplied

Place and taste aversion learning: role of basal forebrain, parietal cortex, and amygdala.

Animals with nucleus basalis magnocellularis (NBM), parietal cortex, dorsolateral frontal cortex, amygdala or control lesions were tested in a neophobia and taste aversion learning task. Only animals with basolateral amygdala lesions were impaired in taste aversion learning and in displaying neophobia to a novel flavor. This finding suggested a dissociation between the function of the NBM component of the basal forebrain cholinergic system and the amygdala. The same animals with NBM or control lesions were then tested for acquisition of a spatial navigation task using a dry-land version (cheese board) of the Morris water maze. Animals with NBM lesions were impaired in this task relative to control animals. Animals with parietal cortex lesions displayed a comparable deficit in the place navigation task. These findings suggest parallel functions for the NBM component of the basal forebrain system and the parietal cortex. The role of the NBM in mediating memory appears to be limited in that it does not play a role in all learning situations.

Amygdala↗

PubMedDate not supplied

Prenatal alcohol exposure alters hippocampal slice electrophysiology.

Pregnant Sprague-Dawley rats consumed an ethanol-containing liquid diet containing 0%, 17.5% or 35% ethanol-derived calories (EDC) from gestation day 8 until parturition. A fourth group was fed standard rat chow as an ad lib diet control. Animals prenatally exposed to ethanol had lower birth weights and impaired passive avoidance learning at 17 days of age. At 90 days of age synaptic potentials in area CA1 were characterized electrophysiologically in hippocampal slices. Slices from ethanol-exposed rats had significantly greater paired-pulse facilitation compared to 0% EDC and ad lib controls. Histological examination of brains from litter mates did not indicate altered number, density or nuclear volumes for neurons in area CA1. These data indicate that prenatal ethanol exposure can result in abnormal hippocampal synaptic physiology and suggest that these changes may contribute to the learning impairments observed in rats following such exposure.

Animals↗

PubMedDate not supplied

Brain MAP-2 phosphorylation is decreased following prenatal alcohol exposure in rats.

The effects of prenatal alcohol treatment on the development and in vitro phosphorylation of specific neuronal phosphoproteins isolated from the frontal cortex and hippocampus of rat brains were studied. In vitro phosphorylation of microtubule-associated protein-2 (MAP-2) was decreased in the frontal cortex but not the hippocampus of animals exposed prenatally to alcohol. Phosphorylation of additional phosphoproteins, including tau proteins, Synapsin I, and GAP-43, was not affected by prenatal alcohol exposure. Littermates of animals used for the phosphorylation assays showed impaired passive avoidance learning. These data demonstrate that the previously reported structural changes in the development of the cerebral cortex following prenatal alcohol exposure and behavioral deficits are accompanied by changes in the phosphorylation of the important cytoskeletal protein MAP-2.

Animals↗

PubMedDate not supplied

Prenatal alcohol exposure attenuates pentylenetetrazol-induced convulsions in rats.

Female rats prenatally exposed to alcohol were tested at 35 days of age for susceptibility to pentylenetetrazol (PTZ)-induced convulsions. There was a significant dose-response effect of PTZ. Contrary to expectations, alcohol-exposed females were slightly but still significantly less convulsion-prone than pair-fed controls. These results suggest prenatal alcohol exposure reduces the susceptibility to convulsions in rats.

Animals↗

PubMedDate not supplied

Prenatal alcohol exposure and the effects of environmental enrichment on hippocampal dendritic spine density.

The effects of environmental enrichment on synaptic spine density in hippocampal area CAI were examined in rats exposed prenatally to alcohol. Pregnant dams were given ethanol via intragastric intubation (6 g/kg/day) from gestational days 8 through 19, or given isocaloric sucrose. An untreated control group was also used. After weaning, offspring from the three groups were then reared for 10 weeks in either isolated (caged alone, not handled) or enriched (group housed with "toys," handled) conditions. Animals were then sacrificed, the brains Golgi impregnated, and CAI pyramidal cell apical and basilar spine densities quantified. Among isolated animals there were no significant differences between control and alcohol-exposed groups. In general, environmental enrichment increased apical or basilar spine densities in untreated and sucrose controls. However, in prenatal alcohol-exposed animals, environmental enrichment did not increase spine densities. Because the environmental enrichment acted postnatally, these findings suggest that the effects of prenatal alcohol exposure included decreased neural plasticity enduring into early adulthood. Such a reduction in neuroanatomical plasticity in hippocampus may be associated with cognitive impairments found following prenatal alcohol exposure.

Animals↗

PubMedDate not supplied

Environmental enrichment and the behavioral effects of prenatal exposure to alcohol in rats.

Animals exposed prenatally to alcohol (4 g/kg/day) via maternal peroral intubation or control offspring were reared after weaning either alone in standard steel/wire cages or in groups of eight, for 6 weeks. Rats exposed prenatally to alcohol and reared in isolation had a dysmetric stride length indicative of an ataxic gait. However, following postweaning environmental enrichment, prenatal alcohol-exposed rats showed no evidence of ataxia. In addition, the prenatal alcohol-exposed rats showed the same magnitude of improved Morris maze performance after enrichment as did the control offspring. These preliminary results suggest that postnatal environment can influence the expression of alcohol-related birth defects in rats, that rats exposed prenatally to alcohol can benefit from the effects of enriched postweaning environment and that postnatal factors can attenuate some of the deficits due to prenatal alcohol exposure.

Animals↗

PubMedDate not supplied

Long-term behavioral effects of prenatal alcohol exposure in rats.

Two studies were conducted to examine the effects of prenatal alcohol exposure on ambulation and head-dipping behavior of rats. The apparatus was a modified "open field" that contained holes in the floor where an animal could "dip" its head. Animals were tested under conditions in which another animal was present in the adjacent box, or the adjacent box was empty. In the first study, 18-month-old rats, prenatally exposed to alcohol, ambulated more and made more head dips than controls when tested with an empty adjacent test box; when there was another animal in the adjacent box, animals prenatally exposed to alcohol did not differ from controls. In the second study, all rats were tested with the adjacent box empty. In this study, 8-month-old rats, prenatally exposed to alcohol, did not ambulate significantly more but did make significantly more head dips than controls. These results indicate that prenatal alcohol exposure has long-term effects on behavior and that some tests (head-dipping) are affected more reliably than others (ambulation). The results also suggest that test conditions may mask these differences.

Analysis of Variance↗

PubMedDate not supplied

Age-related changes in regional cerebral blood flow and behavior in Sprague-Dawley rats.

Studies of regional cerebral blood flow (rCBF) were carried out in male, Sprague-Dawley rats at ages 6, 12 and 24 months. These animals were characterized behaviorally for their ability to learn a complex 14-choice sequential T-maze (i.e., Stone maze) for food reward. Old animals (i.e., 24 month) demonstrated a clear and consistent impairment in maze performance which correlated significantly with decreased cortical blood flow. The results are discussed in relation to cerebral blood flow studies in aging humans and as they relate to the use of rats, the Sprague-Dawley strain in particular, to study brain aging.

Aging↗

PubMedDate not supplied

Effects of prenatal ethanol exposure on hippocampal theta activity in the rat.

This study examined the effects of prenatal ethanol exposure on hippocampal theta activity in adult rats. Subjects were randomly selected from four prenatal treatment conditions: untreated, 0, 3, or 5 g/kg/day ethanol. At approximately 90 days of age, all subjects were surgically implanted with a bipolar electrode in the CA1 region of the hippocampus. Four epochs of hippocampal theta rhythm activity were recorded while the subjects were moving and four more while still, and a normalized theta score was computed and compared among groups. The 5 g/kg male group demonstrated a significantly higher theta score than controls, indicating either an increase in type I (movement-associated) theta and/or a decrease in type II (information-processing) theta activity. These results are consistent with prior reports that prenatal ethanol exposure alters hippocampal function and support clinical indications that monitoring the EEG of children may prove to be useful in the diagnosis of fetal alcohol syndrome and/or the detection of alcohol-related birth defects.

Animals↗

PubMedDate not supplied

Amelioration of fetal alcohol-related neurodevelopmental disorders in rats: exploring pharmacological and environmental treatments.

Fetal alcohol syndrome (FAS) and alcohol-related neurodevelopmental disorders (ARNDs) in children are characterized by life-long compromises in learning, memory, and adaptive responses. Until the advent of effective prevention measures, it will remain necessary to seek ways to treat the life-long neurobehavioral consequences of prenatal alcohol exposure. To date, there are no clinical remedies to recommend for either specific or global fetal alcohol effects. This article reviews our basic research in animal models that assesses the potential of global environmental manipulations or specific psychopharmacological treatments to ameliorate the neurobehavioral effects of prenatal exposure to alcohol. Postweaning environmental enrichment can improve behavioral performance and ameliorate or even eliminate deficits in prenatal alcohol-exposed rats, although there is persistent impairment in neuronal plasticity, as indicated by the failure of hippocampal pyramidal cells to increase dendrite spine density. Behavioral and neural responses to CNS stimulants differ in rats exposed prenatally to alcohol, although it is not clear that these shifts in dose-response curves would predict benefit to children. Although the present results may sound a note of optimism for the development of effective treatment strategies for children with FAS or ARNDs, it is important to consider that application of these findings in rodents may not be straightforward. We also need to know the critical features of specific environments that influence brain development, and the limits of pharmacotherapy, as well as critical periods of exposure. Continued study of the beneficial, ameliorative effects of environmental enrichment, rehabilitative training, and of pharmacological therapies in animal models, will remain a valuable source of information for eventually devising treatments specific for children with FAS and ARNDs.

Animals↗

PubMedDate not supplied

Differential effects of adenosine analogs on amygdala, hippocampus, and caudate nucleus kindled seizures.

This study explored the anticonvulsant effects of adenosine analogs at the focus of seizures kindled from various brain structures. Chemitrodes were implanted in the amygdala (AM), hippocampus (HIPP), or caudate nucleus (CN) of Long-Evans rats and electrically stimulated once daily until fully generalized seizures appeared (i.e., kindled). Once kindled, various doses (0.001-0.5 microgram/0.5 microliter) of the adenosine analogs, L-phenylisopropyladenosine (L-PIA), N-ethylcarboximidoadenosine (NECA) or vehicle were injected into the seizure focus 5 min prior to electrical stimulation. The afterdischarge (AD) and behavioral seizure stages were measured. L-PIA had potent anticonvulsant effects when injected directly into the kindled seizure focus in the AM, HIPP, or CN. NECA effects were statistically significant only in CN-kindled seizures. The regional differences in efficacy of the two adenosine analogs suggest that L-PIA, an A1 adenosine subtype agonist, may exert its effects through A1 adenosine receptors in the AM, HIPP, and CN, where A1 binding has been demonstrated, whereas NECA, an A2 adenosine receptor agonist, may only be maximally effective in the CN where A2 adenosine binding sites are located.

Adenosine↗

PubMedDate not supplied

Magnesium sulfate treatment decreases N-methyl-D-aspartate receptor binding in the rat brain: an autoradiographic study.

OBJECTIVE: We determined the effect of peripherally administered magnesium sulfate on N-methyl-D-aspartate (NMDA) receptor binding capacity in various regions of the rat brain. METHODS: Three separate experiments were performed. 1) Six rats were injected intraperitoneally with 270 mg/kg of magnesium sulfate, followed by 27 mg/kg every 20 minutes for 4 hours; controls (n = 6) received saline. 2) Six rats received intraperitoneal injections of magnesium sulfate (270 mg/kg) every 4 hours for 24 hours, while six received saline. 3) Six rats received intraperitoneal magnesium sulfate (270 mg/kg) every 12 hours for a total of 2 weeks, and six received saline. Rats were subsequently perfused and sacrificed, and their brains were dissected, rinsed, and frozen. Cryostat sections were taken, labeled by in vitro [3H]-CGP 39653, assayed autoradiographically, and mounted on Ultrofilm for 4 weeks. Optical density measurements of binding on each section were performed using an image analyzing system. Eleven brain regions were sampled: 1, 2) frontal and occipital cortex; 3-7) hippocampus--CA-1, CA-3, stratum radiatum, stratum oriens, dentate gyrus; 8) thalamus; 9) hypothalamus; 10) caudate nucleus; and 11) cerebellum. RESULTS: The NMDA receptor binding density in the hippocampus was significantly higher than in all other brain regions in all three experiments. In experiment 1, there was no significant effect on NMDA receptor binding. However, prolonged systemic administration of magnesium sulfate for 24 hours resulted in significantly reduced [3H]-CGP binding in all brain regions sampled. After chronic magnesium sulfate administration (2 weeks), the [3H]-CGP binding was still reduced in the cortex and some regions of the hippocampus; however, there was no significant change in other regions. CONCLUSIONS: Peripheral treatment with magnesium sulfate results in a significant reduction in the NMDA receptor binding capacity in the rat brain. These results support the hypothesis that magnesium central activity is mediated, at least in part, via the NMDA receptor.

Animals↗