Search PubMed⌕ Search

Biomedical subjects

U Ebert

Publications and source records attributed to U Ebert.

At least 55 records · Page 3Linked to original sources
PubMed1999

5'-Nucleotidase activity of mossy fibers in the dentate gyrus of normal and epileptic rats.

Sprouting of mossy fibers in the hippocampus of rats that underwent limbic epileptogenesis by amygdala kindling or kainate injection was studied at the light microscopic and ultrastructural levels by cytochemical demonstration of the enzyme 5'-nucleotidase. This adenosine-producing ectoenzyme has previously been shown to characterize malleable terminals during brain development and lesion-induced synaptogenesis, but to be otherwise associated with glial membranes. At the light microscopic level, kainate-treated but not control or kindled rats showed 5'-nucleotidase activity in the CA3 region and in the inner molecular layer of the dentate gyrus. At the ultrastructural level, in control animals, the synapses of the molecular and granular layers were enzyme negative. Only some mossy fiber boutons of the dentate hilus exhibited 5'-nucleotidase activity. In epileptic rats, synaptic labeling within the hilus appeared more intense. Moreover, 5'-nucleotidase-containing terminals within the inner molecular layer, presumably ectopic mossy fiber boutons, were found in both kindled and kainate-treated rats. It is concluded that, in both the normal and epileptic hippocampus, 5'-nucleotidase is associated with axons capable of a plastic sprouting response. The synaptic enzyme may attenuate the glutamatergic transmission of mossy fibers, in particular of the aberrant mossy fibers in epileptic rats, by producing the inhibitory neuromodulator adenosine. Alternatively, 5'-nucleotidase may influence synapse formation by its putative non-enzymatic, adhesive functions.

5'-Nucleotidase↗
PubMed1999

Characterization of phenytoin-resistant kindled rats, a new model of drug-resistant partial epilepsy: influence of experimental and environmental factors.

It has been recently shown that the variable anticonvulsant effect of phenytoin in the kindling model is not a characteristic of all kindled rats. In a population of amygdala-kindled Wistar rats, subgroups can be selected which consistently respond to phenytoin with an increase in afterdischarge threshold (responders) or which never show such an increase (non-responders). This study examined retrospectively the influence of technical and environmental factors on the results of several prospectively performed phenytoin selections during the last few years. Male and female Wistar rats were implanted with bipolar electrodes aimed at the basolateral amygdala and subsequently kindled. The fully kindled rats were tested for their ability to consistently respond to phenytoin (75 mg/kg i.p.) with an increase of afterdischarge threshold in three consecutive trials. Analysis of 158 Wistar rats of both genders revealed no significant influence of either plasma concentration of phenytoin, kindling parameters, precise electrode location, or differences in focal histology on the result of phenytoin selection. Furthermore, the ability to respond to phenytoin was not associated with the season or the ambient atmospheric pressure during the selection procedure. The data suggest that the difference between phenytoin responders and non-responders is not due to experimental factors, but may rather be genetically determined.

Animals↗
PubMed1999

Characterization of phenytoin-resistant kindled rats, a new model of drug-resistant partial epilepsy: influence of genetic factors.

It has been recently shown that a subpopulation of amygdala-kindled Wistar rats can be selected which do not respond to phenytoin with an increase in afterdischarge threshold (ADT). Such non-responders could be a perfect model for studying the mechanisms of pharmacoresistance of complex partial seizures. Further studies on these rats suggested that the lack of anticonvulsant response was not due to the influence of experimental factors, but is an inherent property of each rat. In this study the influence of genetic factors on the pharmacoresistance to phenytoin by breeding Wistar rats which have been selected for their ability to consistently respond or not respond to phenytoin is examined. Male and female Wistar rats were implanted with bipolar electrodes in the basolateral amygdala and kindled. The fully kindled rats were repeatedly tested for their ability to respond to phenytoin (75 mg/kg i.p.) with an ADT increase. Responders and non-responders were mated and the offspring underwent the same kindling and repeated phenytoin testing procedure. Altogether, four generations of kindled rats were studied. The incidence of responses to phenytoin, i.e. ADT increased by more than 20% of control, was significantly higher in the F2 generation of the responder line compared to the non-responder line, but the number of responders and non-responders in the offspring generations F1-F3 did not significantly increase. The data suggest that the ability to respond or not to respond to phenytoin is genetically determined, although it does not follow a simple scheme of inheritance. The low reproductive success of the kindled and phenytoin-treated rats made it impossible to achieve a strain of phenytoin non-responders.

Animals↗
PubMed1999

Regional drug information service.

BACKGROUND: Drug information centers (DICs) were established in Europe more than two decades ago. The majority of German DICs were created in the 90s. The regional University hospital-based DIC, which offers services to physicans, is now in operation for three and a half years . OBJECTIVE: To evaluate the types of enquiries received and the profile of the users of a drug information service. METHODS: The working procedure at a regional center in Dresden, Germany, is described. The topics for consultation (adverse reactions, pharmacokinetics, etc.) are presented, and the types of drugs involved are classified according to the Anatomical Therapeutic Chemical (ATC) classification. Users are grouped by medical specialty. Future plans for the DIC are discussed. RESULTS: A total of 516 enquiries were received. Questions concerning therapeutic use (34%), adverse drug reactions (28%), pregnancy/lactation (16%), and pharmacokinetics/dosage (15%) were asked most frequently. Cardiovascular drugs (20%), systemic antiinfectives (19%) as well as drugs targeting the central nervous system (15%) and alimentation/metabolism (9%) were the predominant foci of enquiries. The major users of the DIC were internists (19%), general practitioners (19%), pediatricians (18%), and gynecologists (11%). CONCLUSIONS: The types of questions and users of this service were generally similar to those recorded at many other European DICs. The service has begun producing educational bulletins on drug-related topics of clinical relevance.

Drug Information Services↗
PubMed1998

Anticonvulsant effects of melatonin in amygdala-kindled rats.

Different doses of melatonin (50-100 mg/kg i.p.) were tested for their ability to suppress complex partial seizures in the amygdala kindling model of the rat. Thirty minutes after injection of 75 or 100 mg/kg melatonin, the current threshold necessary to elicit epileptic afterdischarges (ADT) was significantly increased by about 200 or 250%, respectively. These doses were also sufficient to suppress generalised seizures at threshold current. All doses of melatonin decreased body temperature by more than 0.5 degrees C, but caused no pronounced ataxia. Seizure susceptibility in terms of ADT changed with the time of the day but seems not to depend on the circadian variation of endogenous melatonin, since the highest ADT was found in the morning when endogenous melatonin levels are low.

Amygdala↗
PubMed1998

Deficient sensorimotor gating following seizures in amygdala-kindled rats.

BACKGROUND: Human patients with limbic epilepsy may develop a psychosis. We combined animal models for epileptogenesis and schizophrenia to investigate possible mechanisms underlying the occurrence of psychoses in epileptics. Since the dysfunction of sensorimotor gating is the basis of some psychotic symptoms, we tested if epileptogenesis or acute seizures influence sensorimotor gating in rats, measured as prepulse inhibition (PPI) of the acoustic startle response (ASR). PPI is the reduction of the ASR that is observed when a startling pulse is preceded by a nonstartling prepulse. Reduced PPI was found in schizophrenics and in rats under certain conditions. METHODS: We investigated the effects on PPI of different models of limbic epileptogenesis (repeated stimulation of the basolateral amygdala, treatment with pentylenetetrazole, injection of kainate). RESULTS: PPI was normal in chronic epileptic rats 1 week after the last generalized seizure. Impaired PPI was found in amygdala-kindled rats 10 min after seizures. The ASR amplitude in the absence of prepulses was increased in kainate-treated rats, but not in the other groups. CONCLUSIONS: Chemical epileptogenesis or repeated stimulation of the amygdala per se did not disrupt sensorimotor gating, but the recent occurrence of seizures in amygdala-kindled rats compromised sensorimotor gating in a way compatible with psychotic states in humans.

Acoustic Stimulation↗
PubMed1998

Differences in the distribution of GABA- and GAD-immunoreactive neurons in the anterior and posterior piriform cortex of rats.

There is accumulating evidence of anterior-posterior differences in the susceptibility of the piriform cortex to seizure induction and to functional alterations in response to seizures elicited from other limbic brain regions, but the reasons for such differences along the anterior-posterior axis of the piriform cortex are not clear. In the present study, GABAergic neurons have been identified in the piriform cortex of the rat at light microscopic level by immunocytochemical localization of GABA and the GABA-synthesizing enzyme glutamic acid decarboxylase. A monoclonal antibody to GABA and, for comparison, polyclonal antibodies to GABA and glutamic acid decarboxylase were used for this purpose. In both anterior and posterior piriform cortex, the highest number and density of GABA-immunoreactive cells was found in layer II. Lower density of GABAergic cells was found in layers I and III and the subjacent endopiriform cortex. When cells were quantified in 19 corresponding sections of the piriform cortex, covering most of anterior-posterior extension of this region, there appeared to be an increased density of GABAergic neurons in sections near to or within the transition zone between anterior and posterior piriform cortex. A more detailed analysis at 4 section levels in the anterior and posterior piriform cortex and the transition zone between the 2 parts substantiated a significantly higher density of GABAergic neurons in the transition zone, which was predominantly due to increased numbers of cells in layers II and III. We propose that the transition zone between anterior and posterior piriform cortex is a location where numerous GABAergic interneurons regulate the activity of neighbouring deep pyramidal cells which receive dense excitatory input from both the olfactory bulb and distant pyramidal cells in the more anterior and posterior parts of the piriform cortex at the same time, thus increasing the risk of paroxysmal activation within this restricted area. This proposal is in line with recent observations of increased susceptibility to epileptiform activation and to kindling-induced neurochemical alterations within the transition zone between anterior and posterior piriform cortex.

Animals↗
PubMed1998

Electrical but not chemical kindling increases sensitivity to some phencyclidine-like behavioral effects induced by the competitive NMDA receptor antagonist D-CPPene in rats.

We have previously reported that a competitive N-methyl-D-aspartate (NMDA) receptor antagonist, DL-[E]-2-amino-4-methyl-5-phosphono-3-pentenoic acid (CGP 37849), produces stereotyped behaviors and hyperlocomotion in amygdala kindled rats at doses which do not induce such phencyclidine (PCP)-like behaviors in nonkindled rats, indicating that kindling predisposes rats to such adverse effects of competitive NMDA receptor antagonists. From these data we predicted that epileptic patients may exhibit a hypersensitivity to PCP-like adverse effects of competitive NMDA receptor antagonists, which was subsequently confirmed in a clinical trial with D-CPPene (SDZ EAA-494; 3-(2-carboxypiperazine-4-yl)propenyl-1-phosphonate). For further exploration of the functional alterations in NMDA receptor responsiveness produced by kindling, we studied whether the enhanced susceptibility of amygdala-kindled rats to PCP-like adverse effects of CGP 37849 is also observed with D-CPPene. Furthermore, we determined whether the enhanced susceptibility of kindled rats to such adverse effects occurs only after relatively short intervals following the last seizure, as used in our previous study, or is a more permanent phenomenon. For this purpose, we compared adverse effects in kindled rats not only with naive (non-implanted) controls, as done in our previous study, but used electrode-implanted nonkindled rats as an additional control to assess the possible bias of mere electrode-implantation. In addition, we studied whether the enhanced susceptibility to NMDA receptor antagonists of electrically kindled rats is also present in chemically kindled animals. In some experiments, the PCP-like uncompetitive NMDA receptor antagonist MK-801 (dizocilpine) was included for comparison. In amygdala kindled rats, D-CPPene produced significantly more stereotyped behaviors than in electrode-implanted or naive nonkindled controls. The enhanced sensitivity of electrically kindled rats to PCP-like stereotypies induced by D-CPPene was observed both 7 and 180 days after the last kindled seizure, indicating a long-lasting if not permanent hypersensitivity to these adverse effects. In addition, more intense circling was observed in amygdala kindled rats, whereas hyperlocomotion only tended to be more intense after D-CPPene in kindled rats. These alterations in D-CPPene-induced behaviors were not observed after chemical kindling with pentylenetetrazole, but D-CPPene induced significantly less hypothermia in chemically kindled rats both 7 and 70 days after the last seizure. The data demonstrate that kindling produces long-lasting alterations in some adverse effects of D-CPPene, substantiating that epileptogenesis as initiated by kindling renders the brain more susceptible to PCP-like behavioral side effects of competitive NMDA receptor antagonists.

Animals↗
PubMed1998

Seizure suppression in kindling epilepsy by grafts of fetal GABAergic neurons in rat substantia nigra.

Compared with studies on models of neurodegenerative diseases, considerably less work has been performed with neural grafts in experimental epilepsy. The potential value of this approach, however, is already shown by evidence that noradrenergic grafts implanted bilaterally into the hippocampus or amygdala-piriform cortex can suppress seizure development in the kindling model of temporal lobe epilepsy. We previously showed that amygdala kindling results in a significant decrease of GABA and its synthesizing enzyme glutamate decarboxylase in substantia nigra (SN), i.e., a region thought to be critically involved in seizure propagation in various models of epilepsy. Thus, transplantation of fetal GABAergic neurons into SN might be an effective means of permanently blocking seizure generalization in kindling epilepsy and probably also other types of epilepsy. To test this hypothesis, three groups of female Wistar rats (n = 10 per group) were kindled by electrical stimulation via a bipolar electrode in the basolateral amygdala. After all rats were fully kindled, one group was implanted with GABA-rich cells prepared from the striatal eminence of Wistar rat fetuses at embryonic day 14. The striatal neurons were bilaterally microinjected at various sites over the anterior-posterior axis of the SN, aimed at the pars reticulata. The second group received microinjections of spinal cord cell preparations, whereas the third group received microinjections of cell-free medium only. In all rats, the threshold for focal discharges (afterdischarge threshold [ADT]) as well as afterdischarge duration and severity and duration of seizures occurring at ADT current were determined once weekly before and after transplantation. Eleven to 12 weeks following transplantation, the rats were killed, and location and integration of grafts were examined by immunohistological methods. Rats with GABAergic grafts in SN exhibited a significant increase in ADT and marked reduction in seizure severity compared with pretransplantation values, whereas no such alteration was seen in the other groups. However, the seizure-suppressing effect of GABAergic grafts was not permanent but slowly disappeared over the weeks after transplantation. Although the data indicate that intranigral transplantation of GABA-producing cells is no effective means of inducing long-lasting anticonvulsant effects in experimental epilepsy, this approach may be an initial step to develop more efficient strategies for seizure suppression.

Animals↗
PubMed1998

Amygdala-kindling induces a lasting reduction of GABA-immunoreactive neurons in a discrete area of the ipsilateral piriform cortex.

Several lines of evidence indicate a critical role of the piriform cortex (PC) in the kindling model of temporal lobe epilepsy, suggesting that the PC is part of an epileptic network that is pivotal in the genesis of kindling, facilitating, and intensifying the spread of seizures from a focus in amygdala, hippocampus, or other limbic brain regions to cortical and subcortical regions. Kindling of the amygdala has been shown to induce long-lasting changes in synaptic efficacy in the ipsilateral PC comparable to abnormalities seen in epileptic foci, but the neurochemical alterations possibly underlying these functional changes are not known. The possibility that the enhanced excitability of the PC in response to kindling is related to a reduction of GABAergic neurotransmission prompted us to examine if a lasting reduction in GABA-immunoreactive PC neurons is detectable after kindling of the basolateral amygdala (BLA) in rats. Furthermore, GABA immunoreactivity was determined in the BLA in order to investigate whether GABAergic neurons decrease in focal tissue, as previously suggested by neurochemical and immunocytochemical studies in amygdala-kindled rats. Three groups of age-matched rats were used: (1) a group of rats that was kindled via electrical stimulation by a bipolar electrode implanted in the right BLA, (2) a group of BLA-implanted but nonstimulated rats, and (3) a group of non-implanted, naive control rats. The kindled rats were sacrificed 40 days after the last fully kindled seizure. The two other groups of rats were sacrificed together with the kindled rats on the same days, and tissues from kindled and control rats were treated concurrently throughout the immunohistochemical analysis. GABA neurons were stained by a monoclonal antibody to GABA. Kindling of the BLA led to a pronounced decrease in the number of GABA immunoreactive neurons in the ipsi- and contralateral BLA at all section levels examined. In the PC, no significant differences between groups were seen in the contralateral hemisphere, while a significant reduction in GABA immunoreactive cells was observed in the transition zone between anterior and posterior PC in the hemisphere ipsilateral to the BLA electrode. The present findings add to the accumulating evidence that the PC is critically involved in kindling-induced epileptogenesis. The data furthermore substantiate that the PC is not a homogeneous structure but that there are differences along the anterior-posterior axis of this region in neurochemical (and most certainly also functional) consequences in response to kindling stimulation from other limbic brain regions.

Amygdala↗
PubMed1998

Pharmacokinetics and pharmacodynamics of scopolamine after subcutaneous administration.

The effects of subcutaneously administered scopolamine on quantitative electroencephalogram (qEEG) and cognitive performance were evaluated and correlated with pharmacokinetic parameters in a randomized, double-blind placebo-controlled crossover study of 10 healthy male volunteers. Changes in qEEG and cognition were determined for 8 hours after drug administration. Scopolamine produced dose- and time-dependent impairments of attention and memory and a time-dependent increase in delta power (1.25-4.50 Hz) and a decrease in fast alpha power (9.75-12.50 Hz) on qEEG compared with placebo. Maximum serum concentrations of scopolamine occurred 10 to 30 minutes after drug administration. Mean peak serum concentrations (free base) were 3.27, 8.99, and 18.81 ng/mL after administration of 0.4, 0.6 mg, and 0.8 mg scopolamine, respectively. Elimination half-life was approximately 220 minutes. The findings indicate temporary changes in qEEG and psychometric tests, and support the possible use of such a testing model for impaired cognitive functions such as age-related memory disturbances.

Adult↗
PubMed1998

Differences in kindling development in seven outbred and inbred rat strains.

The kindling phenomenon, i.e., the progressive development of focal and secondarily generalized seizures upon repeated electrical stimulation of a limbic brain region, occurs in various species, but with marked differences in kindling rate between species and also within the same species. In rats, differences in kindling rates have been reported within the same strain and between different strains, and both genetic and environmental influences are thought to be involved in this variability. In most studies on kindling in rats, outbred strains such as Sprague-Dawley have been used. In the present study, we compared rates of amygdala kindling development in two outbred (Sprague-Dawley, Wistar) and five inbred (Lewis, Fischer 344, ACI, Wistar-Kyoto, Brown Norway) rat strains, including several strains which have not been kindled before. We were particularly interested which parts of the stepwise progression of kindling differ among these strains. Furthermore, the sensitivity of the basolateral amygdala to electrical stimulation was determined before and after kindling. Once daily electrical stimulation of the basolateral amygdala resulted in marked interstrain differences in kindling rates, with Sprague-Dawley and Brown-Norway rats exhibiting the lowest number of stimulations to reach fully kindled (stage 5) seizures, and Lewis rats showing the highest number of the 7 strains. In contrast to the significant differences in number of stimulations to reach the fully kindled state, total (cumulative) afterdischarge duration (ADD) to reach stage 5 did not significantly differ among strains, substantiating that cumulative AD is the principal factor in the acquisition of kindled seizures. Marked differences in ADD of a stage 5 seizure were obtained between strains, with strains kindling rapidly exhibiting longer ADD than strains kindling slowly. Postkindling afterdischarge threshold (ADT) varied significantly among strains, but only 3 of the 7 strains showed a decrease of ADT compared to prekindling values. When the stepwise progression of kindling was evaluated, pronounced interstrain differences were determined in the time spent in the initial phase of kindling, i.e., stage 1 seizures, both in terms of stimulations and cumulative ADD, indicating that variations in kindling rates were predominantly due to the time needed to progress from stage 1 to subsequent stages of the kindling process. The data seem to indicate that inbred rat strains offer an interesting resource for dissecting the underlying genetic basis for phenotypic differences in epileptogenesis as induced by kindling, although the high variability of kindling rates seen within some inbred strains weakens this possibility.

Amygdala↗
PubMed1998

Dilatory effects of phosphodiesterase inhibitors on human hand veins in vivo.

OBJECTIVE: To compare the venodilator potencies of the phosphodiesterase (PDE) III inhibitors amrinone and enoximone with the unspecific PDE inhibitors theophylline and pentoxifylline in human hand veins in vivo. METHODS: Eighteen healthy nonsmokers (16 men and two women) were studied using the dorsal hand vein technique. After preconstriction with the selective alpha1-adrenergic-receptor agonist phenylephrine dose-response curves were constructed for amrinone (1-270 microg x min(-1)), enoximone (1-270 microg x min(-1)), theophylline (5-1500 microg x min(-1)) and pentoxifylline (2-877 microg x min(-1)) in a random order on separate occasions. Due to limitation in the maximum dose infused in order to avoid systemic effects, full dose-response curves could not be constructed for pentoxifylline. In this case, the individual dose of pentoxifylline and theophylline producing 50% venodilation were compared. RESULTS: All PDE inhibitors induced dose-dependent venodilation. The value of maximum venodilation was the same for amrinone, enoximone and theophylline. The infusion rate needed to induce 50% of maximum venodilation (ED50) was not significantly different for amrinone (geometric mean, 8.8 microg x min(-1)) and enoximone (14.2 microg x min(-1)), whereas the ED50 of theophylline (84.0 microg x min(-1)) was significantly higher than either amrinone or enoximone. The dose necessary to dilate the vein to 50% the maximum dilation (as determined during sodium chloride infusion) was significantly higher for pentoxifylline than for theophylline (409 vs 71 microg x min(-1)). CONCLUSIONS: These findings demonstrate that enoximone and amrinone have similar venodilatory potency which is six times higher than that of theophylline. The least potent vasodilator in this study was pentoxifylline.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1998

Anticonvulsant effect of fosphenytoin in amygdala-kindled rats: comparison with phenytoin.

Phenytoin has been reported to exert variable anticonvulsant effects in the kindling model of complex partial seizures. Phenytoin is only water soluble at a pH of more than 10, and it has been suspected that poor absorption of the drug is responsible for its lack of effect in some experiments. Recently, fosphenytoin, a prodrug of phenytoin, has been developed by phosphorylating phenytoin which makes the drug water soluble at physiological pH while it is rapidly transformed to phenytoin after injection. This study examined the anticonvulsant profile and the absorption after intraperitoneal injection of fosphenytoin, compared to its parental drug phenytoin. The pharmacokinetic parameters of phenytoin and fosphenytoin were compared by determining plasma levels of phenytoin after i.p. injection of 50 mg/kg phenytoin or the equivalent dose of 84 mg/kg of fosphenytoin in non-kindled female Wistar rats. After both injections the maximal plasma concentration of phenytoin was about 30 microg/ml. The relative bioavailability of fosphenytoin was 83%. In contrast to phenytoin, failed injections resulting in non-detectable plasma concentration of phenytoin were almost absent after fosphenytoin. In fully kindled female Wistar rats, fosphenytoin dose-dependently increased the focal seizure (afterdischarge) threshold. Seizure severity and duration at threshold were reduced only after the highest does of fosphenytoin tested (84 mg/kg). Thus, fosphenytoin showed anticonvulsant properties similar to phenytoin in amygdala kindled rats. We conclude that fosphenytoin is an adequate and reliable substitute for the parenteral injection of phenytoin in experimental seizure models of rats.

Amygdala↗
PubMed1998

Limbic epileptogenesis alters the anticonvulsant efficacy of phenytoin in Sprague-Dawley rats.

Studies on the anticonvulsant efficacy of the major antiepileptic drug phenytoin in kindled rats have often reported inconsistent effects. It has been proposed that technical and genetic factors or poor and variable absorption of phenytoin after i.p. or oral administration may be involved in the lack of consistent anticonvulsant activity of phenytoin in this model of temporal lobe epilepsy. We examined if kindling itself changes the anticonvulsant efficacy of phenytoin by testing this drug before and after amygdala kindling in male and female Sprague-Dawley rats. To exclude the possible bias of poor and variable absorption, blood was sampled in all experiments for drug analysis in plasma. The threshold for induction of focal seizures (afterdischarge threshold; ADT) was used for determining phenytoin's anticonvulsant activity. Before kindling, phenytoin, 75 mg/kg i.p., markedly increased ADT in both genders, although the effect was more pronounced in males. Following kindling, the anticonvulsant activity obtained with phenytoin, 75 mg/kg, before kindling was totally lost, and female rats even exhibited a proconvulsant effect upon administration of this dose, indicating that kindling had dramatically altered the anticonvulsant efficacy of phenytoin. Plasma levels of phenytoin were comparable before and after kindling, and were within or near to the 'therapeutic range' known from epileptic patients. When the dose of phenytoin was reduced to 50 or 25 mg/kg i.p., significant anticonvulsant effects on ADT were obtained. When phenytoin, 50 mg/kg, was administered i.p. or i.v. in the same group of fully kindled rats, both anticonvulsant activity and plasma drug levels were comparable with both routes, indicating that the i.p. route is suited for such studies. The data indicate that kindling alters the dose-response of phenytoin in that a high anticonvulsant dose becomes ineffective or proconvulsant after kindling, possibly by an increased sensitivity of the kindled brain to proconvulsant effects of phenytoin which normally only occur at much higher doses. If similar alterations evolve in humans during development of chronic epilepsy, this may be involved in the mechanisms leading to intractability of temporal lobe epilepsy.

Amygdala↗
PubMed1998

Scopolamine model of dementia: electroencephalogram findings and cognitive performance.

BACKGROUND: Memory and cognitive functions are known to decline with advancing age. Studies have suggested that this may be due to a decrease in cholinergic function in the brains of elderly people. This review aims to assess studies documented in the literature dealing with the 'scopolamine model' of dementia. METHODS: Sources included MedLine searches from the last 10 years (search for 'scopolamine model', 'dementia', 'electroencephalogram', 'cognition') and references from original and review articles. The aim was to include human and animal studies occupying the cholinergic hypothesis in cognitive dysfunction. Electroencephalographic (EEG) and cognition findings were considered. RESULTS: Scopolamine influences delta, theta, alpha and beta activity in EEG and partially mimics the EEG changes found in patients with senile dementia or dementia of the Alzheimer type. Effects on different cognitive functions have been extensively documented. CONCLUSION: Scopolamine produces similar memory deficits seen in the elderly, but the drug cannot induce the full range of deficits seen in patients with Alzheimer's disease. Various aspects of memory were unaffected by scopolamine administration. Memory improvements in elderly subjects can be achieved after cholinergic stimulation.

Aged↗