Biomedical subjects

R F Berman

Publications and source records attributed to R F Berman.

At least 37 records · Page 2Linked to original sources

PubMed1992

The A2-selective adenosine analog, CGS 21680, depresses locomotor activity but does not block amygdala kindled seizures in rats.

The actions of the highly selective A2 adenosine agonist, CGS 21680, in modulating kindled seizures and locomotor activity were examined. I.c.v. injections of CGS 21680 into the lateral cerebral ventricle in fully kindled rats were found to prolong the period of postictal EEG depression and reduce postictal spiking in a dose-dependent manner, while not affecting the behavioral seizure stage or afterdischarge duration. CGS 21680 injections also lead to a dose-related inhibition of locomotor activity in rats exposed to an open field apparatus compared to rats receiving control injections of saline. These observations implicate the involvement of the A2 adenosine receptor in postictal phenomena and the locomotor depressant actions of adenosine, but do not indicate a direct anticonvulsant activity following A2 activation.

Adenosine↗

PubMed1992

Peripheral magnesium sulfate enters the brain and increases the threshold for hippocampal seizures in rats.

OBJECTIVES: Our objectives were to determine whether magnesium sulfate crosses the blood-brain barrier and whether it has central anticonvulsant action. STUDY DESIGN: In experiment 1 34 female Long-Evans rats were divided into six groups: control (n = 7); single magnesium sulfate injection and evaluation after 20 minutes in 3 conditions: normal rats (n = 7), sham-operated animals (n = 5), and after electrical stimulation by hippocampal electrode (n = 5); single injection and evaluation after 2 hours (n = 5); and prolonged (2 hours) serum magnesium elevation (n = 5). Serum, cerebrospinal fluid, and specific brain areas were analyzed for magnesium concentrations. In experiment 2 threshold for electrical seizure was measured in eight rats before and after intraperitoneal injections of magnesium sulfate versus saline solution. RESULTS: In experiment 1 there was a significant correlation between blood and cerebrospinal fluid magnesium concentrations (r = 0.80, p < 0.0001). Magnesium concentrations were increased in the cortex and hippocampus, with the largest changes occurring after two hours of sustained serum magnesium concentrations (p < 0.01). Induction of hippocampal seizure activity resulted in further elevations in cerebrospinal fluid magnesium concentrations but did not change brain concentrations. In experiment 2 magnesium sulfate increased the electrical threshold required to induce seizures by 34% (p = 0.01). CONCLUSIONS: Magnesium sulfate enters the cerebrospinal fluid and brain and has a central anticonvulsant effect.

Animals↗

PubMed1992

Cerebrovascular responses to pentylenetetrazol: time and dose dependent effects.

The effects of subconvulsant and convulsant doses of pentylenetetrazol (PTZ) on cerebral blood flow (rCBF), permeability-capillary surface area products (rPS), and brain vascular spaces (BVS) were examined in 15 brain regions at 1 h, 24 h and 1 week after injection in male Sprague-Dawley rats. Brain histology was examined 3 days after injection. A dose of PTZ (50 mg/kg, i.p.), sufficient to trigger a single convulsive seizure, produced small regional changes in rCBF at 1 h, but not at 24 h or 1 week after injection. No significant changes in rPS or BVS were found at any time, and only mild histologic changes were observed. In contrast, a dose of PTZ (25 mg/kg) which failed to cause either convulsions or significant electrocorticographic changes, markedly increased rCBF and rPS. Some of these regional effects were still observed 1 week later. Similarly, more severe and extensive cellular changes followed treatment with the subconvulsive dose. These findings indicate that PTZ treatment can have prolonged effects on cerebrovascular functions and neuronal integrity even in the absence of convulsive activity.

Analysis of Variance↗

PubMed1992

Anticonvulsant effects of magnesium sulfate on hippocampal seizures: therapeutic implications in preeclampsia-eclampsia.

OBJECTIVE: The objective of this study was to determine whether magnesium sulfate has central anticonvulsant effects. STUDY DESIGN: In three experiments we investigated the anticonvulsant properties of magnesium sulfate on the hippocampus because of its high density of N-methyl-D-aspartate receptors and link to clinical epilepsy. Seizure activity was elicited in the hippocampus of rats or in in vitro hippocampal brain slices. The effects of magnesium on seizure activity were determined. RESULTS: (1) Intraperitoneal magnesium sulfate (270 or 360 mg/kg) failed to block hippocampal seizures but reduced electroencephalographic amplitude and seizure duration. (2) Injection of magnesium sulfate directly into a seizure focus blocked seizures and elevated seizure thresholds. (3) Low magnesium levels produced epileptiform activity in an in vitro hippocampal brain slice preparation; the epileptiform activity was reversed by increasing the magnesium concentration. CONCLUSIONS: Magnesium sulfate has central anticonvulsant activity on hippocampal seizures, implicating the N-methyl-D-aspartate receptor in eclamptic seizures and in the therapeutic efficacy of magnesium sulfate.

Animals↗

PubMed1992

Audiogenic seizure susceptibility and auditory brainstem responses in rats prenatally exposed to alcohol.

Rats prenatally exposed to alcohol (0%, 17.5%, or 35% ethanol-derived calories) were tested for audiogenic seizure susceptibility on one of postnatal days 18 to 23, then retested 5 days later. Prenatal alcohol exposure did not influence audiogenic seizure susceptibility or severity. There was, however, a significant increase in seizure incidence on the retest day for all groups, suggesting a priming effect. Auditory brainstem response (ABR) data suggested that prenatal alcohol exposure and acoustic trauma (i.e., exposure to an alarm bell used for eliciting audiogenic seizures) induced measurable sensorineural hearing loss, and that the combined exposure to alcohol and acoustic trauma interacted additively to produce greater hearing loss than either alone.

Animals↗

PubMed1991

Functional activity of the adenosine binding enhancer, PD 81,723, in the in vitro hippocampal slice.

The adenosine receptor binding enhancer, PD 81,723, enhances the inhibitory effects of exogenously applied adenosine in a dose-dependent manner in hippocampal brain slices. Extracellular recordings were obtained from the CA1 cell layer while electrically stimulating the stratum radiatum. Application of 1, 10 or 32 microM PD 81,723 in the presence of adenosine resulted in a dose-dependent reduction in the amplitude of the population spike which could be partially reversed by theophylline. In addition, hippocampal slices exposed to adenosine showed greater paired-pulse facilitation compared to control and this facilitation was significantly enhanced by the presence of PD 81,723. PD 81,723 had no effect when administered alone, but required the presence of adenosine. These results demonstrate that in addition to enhancing adenosine receptor binding, PD 81,723 also enhances the functional activity of adenosine in the hippocampal slice.

Adenosine↗

PubMed1991

Chronic theophylline treatment in vivo increases high affinity adenosine A1 receptor binding and sensitivity to exogenous adenosine in the in vitro hippocampal slice.

The present investigation examined the effects of chronic treatment with the adenosine receptor antagonist theophylline in vivo, on in vitro hippocampal electrophysiology and adenosine A1 receptor binding in the same animals. Adult rats were injected once daily (i.p.) with theophylline for 1 week at 75 mg/kg, followed by an additional week at 100 mg/kg, or with saline for the same 2-week period. Two days following the last injection, hippocampal slices were prepared and population spikes recorded from the pyramidal cell layer of area CA1 were elicited by Schaffer collateral-commissural fiber stimulation. The degree of inhibition caused by superfused adenosine was compared between hippocampal slices from theophylline- and saline-treated rats. Tissue from the contralateral hippocampus was used in [3H]cyclohexyladenosine ([3H]CHA) receptor binding. Hippocampi from theophylline-treated animals showed a significantly greater number of [3H]CHA binding sites (apparent Bmax; 125% of control, P less than 0.05), without a significant change in binding affinity, and were more sensitive than controls to the inhibitory effects of adenosine on the population spike response. These results suggest that chronic adenosine receptor antagonism results in the up-regulation of adenosine A1 receptors which are functional and physiologically relevant in the in vitro hippocampus, and further supports the hypothesis that methylxanthine tolerance is mediated, at least in part, by an increase in adenosine receptor density.

Adenosine↗

PubMed1991

Chronic theophylline treatment increases adenosine A1, but not A2, receptor binding in the rat brain: an autoradiographic study.

Chronic exposure to adenosine receptor antagonists results in an upregulation of brain adenosine A1 receptors as measured by traditional radioligand binding techniques. In the present study, quantitative receptor autoradiography was used to characterize alterations in rat brain adenosine A1 and A2 receptors following the repeated administration of high doses of theophylline. Daily administration of theophylline (75 or 100 mg/kg) markedly increased (125-150% of control) 1 nM [3H]cyclohexyladenosine binding to adenosine A1 receptors in specific cellular layers of the hippocampus, thalamus, and cerebellum with other brain regions showing more moderate increases in binding. By contrast, this chronic theophylline treatment did not produce any significant alterations in the binding of 4 nM [3H]CGS 21680 to adenosine A2 receptors, which were exclusively localized in the striatal region. This apparent differential sensitivity of adenosine receptor subtypes to chronic antagonist treatment suggests a possible intrinsic difference in the regulation of these receptor subtypes which may also be specific to particular brain regions. These results are discussed in relationship to other recent observations, indicating that the pattern of agonist binding to adenosine receptors may be regulated by a differential extent of coupling between adenosine receptors and G-binding proteins in different brain regions.

Adenosine↗

PubMed1990

Adenosine involvement in postictal events in amygdala-kindled rats.

The actions of adenosine in modulating amygdala kindling were examined using the stable adenosine analog 5'-N'-ethylcarboxamidoadenosine (NECA) and caffeine, an adenosine antagonist. Systemically administered NECA was found to significantly reduce the rate of postictal spiking and to significantly increase the duration of postictal EEG depression in amygdala kindled rats. In contrast, systemically administered caffeine significantly increased kindled seizure duration and reduced the duration of postictal EEG depression. Systemic administration of the methylxanthine derivative, 8-sulfophenyl theophylline (8-PST), failed to block the effects of NECA on kindling. Since systemically administered 8-PST blocks peripheral adenosine receptors, but has only limited CNS activity, the effects of NECA appear to be centrally mediated. These observations further demonstrate a role for adenosine in postictal phenomena and support the hypothesis that a release of endogenous adenosine contributes to the termination of ongoing seizure activity.

Adenosine↗

PubMed1989

The effects of p-chloroamphetamine, a depletor of brain serotonin, on the performance of rats in two types of positively reinforced complex spatial discrimination tasks.

Learning in male Sprague-Dawley rats was assessed in two types of positively reinforced complex spatial discrimination tasks (Stone 14-unit T-maze and eight-arm radial-arm maze) following cytotoxic lesions of central serotonergic terminal projection fields with p-chloroamphetamine (PCA). Learning, as expressed as mean number of errors per day and mean number of trails required to reach criterion, was significantly enhanced in the PCA-lesioned animals trained in the Stone maze. On the other hand, the performance of the PCA-lesioned animals trained in the eight-arm radial-arm maze was not found to differ significantly from that of saline-injected animals. The improved acquisition of the PCA-lesioned rats trained in the Stone maze was completely abolished following pretreatment with the selective serotonergic reuptake inhibitor norzimeldine. Neurochemical analyses of the brains of representative animals revealed that the levels of serotonin and its major metabolite, 5-hydroxy-3-indoleacetic acid, were both significantly reduced by PCA in all regions examined. While it is clear from these and other studies that the serotonergic nervous system plays an important role in the processes underlying learning and memory, these results further underscore the selective role of this neurotransmitter system in the way information is processed by the brain.

Amphetamines↗

PubMed1989

Association of sleep parameters and memory in intact old rats and young rats with lesions in the nucleus basalis magnocellularis.

Relations between sleep and memory were examined as a function of aging in rats. Sleep (24 hr), passive avoidance retention, and choline acetyltransferase (CAT) activity were assessed in 3 age-groups (6, 15, and 24 months old). Age-related alterations were evident in sleep, memory, and cortical and striatal CAT activity. Retention deficits in old rats were significantly correlated with several measures of paradoxical sleep. Similar analyses in 6- and 15-month-old rats with ibotenic acid-induced lesions of the nucleus basalis magnocellularis (NBM) showed several alterations in sleep, memory, and cortical CAT activity comparable to those seen in the old rats. One measure of paradoxical sleep, bout duration, correlated significantly with retention scores in rats with lesions. Thus, fragmented paradoxical sleep accompanies memory impairments in old rats and in young rats with NBM lesions.

Aging↗

PubMed1988

Persisting behavioral and neurochemical deficits in rats following lesions of the basal forebrain.

The effects of excitotoxic lesions of the nucleus basalis magnocellularis on cortical cholinergic activity and passive avoidance performance were examined in rats at 6, 14, 84 and 180 days after lesioning. Lesioned rats showed significant impairment of passive avoidance retention at every time point tested, with no evidence of behavioral recovery compared to unoperated and sham-lesioned (i.e., vehicle-injected) control rats. Cortical choline acetyltransferase (CAT) activity was reduced relative to controls at all time points examined, with the greatest reduction (i.e., 28%) occurring at approximately 14 days after lesioning. The levels of CAT activity at 180 postlesioning remained reduced compared to control animal levels, but less so than at 14 days after lesioning, indicating partial recovery. No changes in cholinergic muscarinic binding were observed at any time following lesioning. The results indicate that the behavioral and neurochemical effects of NbM lesions persist for at least 6 months following lesioning, but that partial, gradual recovery of cholinergic activity occurs.

Animals↗

PubMed1988

Atropine slows olfactory bulb kindling while diminished cholinergic innervation does not.

The development of kindled seizures elicited through electrical stimulation of the rat olfactory bulb (OB) was examined under two conditions which decrease cholinergic neurotransmission. Atropine sulfate (25 mg/kg, IP) administered 1 hr prior to stimulation of the OB was found to significantly delay the acquisition of the fully kindled state. In a second experiment, diminished cholinergic innervation of the OB was established using chemical lesions of the basal forebrain cholinergic system. Despite the depletion of acetylcholine (Ach), as determined by acetylcholinesterase (AchE) and choline acetyltransferase (ChAt) assays, no significant alterations in kindling parameters were observed. Based upon these findings we suggest that Ach is not critical to the establishment of an OB kindled focus but is important for the propagation and generalization of epileptiform activity initiated through OB stimulation.

Acetylcholinesterase↗

PubMed1987

ACTH-related peptides, kindling and seizure disorders.

Very small amounts of pituitary hormones and their peptide fragments can profoundly affect learning, memory and other behaviors in both rodents and humans. In addition, several potent pituitary hormone analogs have been developed (e.g. ORG-2766) which retain the behavioral but not the endocrine properties of the parent hormone. The abilities of these peptides to influence nervous system functions suggested that they also may be capable of modifying seizure activity. This possibility is supported by the fact that treatment with adrenocorticotropic hormone (ACTH) represents a major effective therapy for at least one clinical convulsive disorder, infantile spasm. This contention also is reinforced by our findings that ORG-2766 markedly reduces both the behavioral severity and the spread of seizure potentials in an animal model of epilepsy, the kindled rat. By contrast, arginine vasopressin and its non-endocrine desglycyl fragment (DGAVP) facilitates the seizure process in this animal model. Our research also suggests that the behavioral and physiological effects of certain anterior and posterior pituitary hormone fragments depend, in part, on their abilities to modulate permeability mechanisms in brain vasculature. In addition, and especially significant from the standpoint of etiology, is the observation that the kindling process itself appears to alter cerebrovascular permeability. In the kindled rat, "permanent" decreases in permeability (60-75%) are found selectively in the hypothalamic and hippocampal regions, weeks after the last seizure. Several lines of evidence indicate that disruption of normal cerebrovascular function occurs following epileptiform seizures. We propose that an immediate increase in cerebral blood flow and cerebrovascular permeability occurs following a single, acute seizure, and that repeated chronic seizures lead to damage to the cerebrovascular system. Sustained damage would be expected to contribute to the development and maintenance of a chronic seizure focus. Such observations suggest a link between important cerebrovascular disturbances associated with seizures and the existing known and proposed electrophysiological, metabolic and neuropathological substrates of epilepsy. They also point to new strategies for the treatment of seizure disorders by focusing on ways to reduce or prevent cerebrovascular damage.

Adrenocorticotropic Hormone↗

PubMed1985

Amygdala kindled seizure stage is related to altered benzodiazepine binding site density.

Benzodiazepine receptor binding was examined in rats at 3 stages of amygdaloid kindling (i.e., initial afterdischarge, Stage 3 and Stage 5) immediately or 24 hr after seizure. 3H-diazepam binding site density (Bmax) was significantly increased 24 hr after Stage 3 and Stage 5 kindled seizures in the hippocampus but not in the amygdala. There were no significant differences in the dissociation constants (KD) between kindled and control rats at any time point examined for either brain region. These results demonstrate that changes in benzodiazepine binding are observed with partial kindled seizures (i.e., Stage 3), indicating that generalized seizures are not prerequisite to increased benzodiazepine receptor site density.

Amygdala↗

PubMed1985

Prolonged postictal depression in amygdala-kindled rats by the adenosine analog, L-phenylisopropyladenosine.

Studies have shown that adenosine analogs may modulate kindled seizures. The present study demonstrated that systemic administration of the adenosine analog, L-phenylisopropyladenosine (L-PIA), substantially prolonged the postictal depression and decreased the frequency of spiking that follows amygdala-kindled seizures in rats. Fully kindled rats were administered L-PIA (0.1 to 2.0 mg/kg, i.p.) or saline 30 min before stimulation of the amygdala. Afterdischarge durations with L-PIA did not differ from those with saline, and behavioral seizures were only slightly decreased in severity with 2.0 mg/kg L-PIA. However, 0.5 to 2.0 mg/kg L-PIA increased the duration of the postictal depression by more than 20 min and, at 2.0 mg/kg, L-PIA decreased the frequency of postictal spiking. Postictal administration of caffeine (32 mg/kg, i.p.) reversed the prolongation of the postictal depression induced by 1.0 mg/kg L-PIA. These effects did not seem to be mediated by peripheral actions of L-PIA (i.e., lowered blood pressure) as hydralazine, which decreases blood pressure through peripheral mechanisms, did not affect ictal or postictal events. These results indicate that adenosine may modulate neuronal excitability that follows kindled seizures.

Adenosine↗

PubMed1985

Age of testing as a factor in the behavioral effects of early lead exposure in rats.

The behavioral effects of postnatal administration of lead during weaning were tested in young and adult rats. Rats received either 10 mg/kg IP lead acetate or equimolar sodium acetate daily for the first twenty days of life. Tests of performance on an 8-arm radial maze and a passive avoidance task were begun at 25 days after birth or 90 days after birth. Lead-treated rats did not perform significantly different than control rats on the radial arm maze at either age tested. Young lead-treated rats performed with significantly longer lick latencies than young control rats on the passive avoidance task. Adult lead-treated rats performed with shorter food latencies than adult control rats. A group of young rats was retested on the passive avoidance task at 150 days after birth. Performance on the retest was similar to their early performance. Differences in performance of young and adult lead-treated animals on the passive avoidance task are discussed in terms of an interaction of the effects of lead exposure, maturation, and early experience.

Age Factors↗

PubMed1985

Further characterizations of the nature of the behavioral and neurochemical effects of lesions to the nucleus basalis of Meynert in the rat.

Converging lines of evidence indicate an important role for the basal forebrain cholinergic system in memory processes. The principal origin of the cholinergic projection to the neocortex appears to be the magnocellular neurons in the region of the nucleus basalis of Meynert (NbM). We examined the effects of bilateral lesions of the NbM on retention of shock avoidance training by stereotaxically injecting rats with 0.5 microliter of ibotenic acid (14 micrograms/microliter) into the NbM. Two weeks later rats were given passive avoidance training and tested for retention of the original avoidance habit 5 min, 30 min, or 24 hr later. Rats with lesions of the NbM showed significantly impaired shock avoidance performance compared to non-operated controls at both 30 min and 24 hr, but not at 5 min after training. Lesioned animals also showed a significant decrease in cortical choline acetyltransferase (CAT) and acetylcholinesterase (AChE) activities. No differences in muscarinic receptor binding or plasma cholinesterase activity was observed. The results demonstrate the usefulness of NbM lesions as a model for studying the role of the basal forebrain cholinergic system in memory processes.

Acetylcholinesterase↗