Age-related differences in MK-801- and amphetamine-induced locomotor and stereotypic activities of rats.

Changes in locomotor and stereotypic activities induced by an i.p. injection of either (+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d)-cycloheptan-5,10-imine maleate (dizocilpine or MK-801; 0.3 mg/kg) or D-amphetamine sulfate (AMPH; 1.5 mg/kg) were studied in male Mill Hill hooded rats of different age. The following age groups of animals were considered: 28-30 postnatal day (PND)-old rats (peripubertal), 48-50 PND-old (pubertal), 3-month-old (adults), 12-month-old (middle-aged) and 24-month-old (aged). The motor response was measured by an automated animal activity measuring system. The obtained results showed that: (1) in contrast to AMPH, MK-801 induced more pronounced increases of both locomotor and stereotypic activities in peripubertal and pubertal than in adult and aged rats; (2) AMPH induced the same locomotor and stereotypic activity increase in pubertal, adult and middle-aged rats; (3) both AMPH and MK-801 led to a senescence-related decrease of motor activity. These data suggest that the balance of the glutamatergic and dopaminergic systems changes during aging. Such a change is important in understanding schizophrenia and the motor system decline observed in the later stages of life.

Differential effects of amphetamine and phencyclidine on the expression of growth-associated protein GAP-43.

The purpose of the present study was to test changes in the expression of growth-associated protein (GAP-43) after chronic treatment with two different psychotomimetic drugs: amphetamine and phencyclidine. Rats were treated chronically for 7 days (twice daily) with 5 mg/kg of amphetamine and phencyclidine and sacrificed after 2, 5 or 7 days of treatment, and following 7, 14 or 21 days of recovery after full treatment (7 days). Separate groups of rats were treated on the same regiment with haloperidol, and control group was treated with vehicle. To determine the effects of different psychotomimetic drugs on the expression of GAP-43 we have used Northern blotting and quantitative in situ hybridization. Treatment with amphetamine induced decrease of GAP-43 mRNA expression, that was detected also during recovery period, up to 14 days after the last day of 7 days treatments. On the contrary, PCP induced increase of GAP-43 mRNA expression, that was detectable from the first days of treatment until 21 days after the last day of treatment. Treatment with haloperidol did not produce significant changes in GAP-43 mRNA expression. It can be suggested that GAP-43 upregulation upon phencyclidine treatment occurs as a result of functional activation of pathways able to participate in remodeling, while amphetamine showed neurotoxic effect, decreasing expression of GAP-43 mRNA.

Apoptosis induction by phencyclidine in the brains of rats of different ages.

We examined whether acute administration of phencyclidine (PCP), an antagonist of the N-methyl-D-aspartate (NMDA) receptor-channel complex, can cause neuronal toxicity that is associated with apoptosis. Three- and 24-month-old rats were placed in locomotor activity chambers. PCP (50 mg/kg) or saline (0.15 M NaCl) were simultaneously administered to the treated and age-matched controls. After observing changes of locomotor activities, the animals were killed 24 h after treatment. The brains were processed for in situ analysis of apoptosis either by propidium iodide (PI) staining, or for the terminal dUTP nick-end labelling (TUNEL) method. The regional distribution of apoptotic nuclei was established using PI staining. Apoptosis was additionally confirmed and quantified by the TUNEL technique. PI and TUNEL staining revealed that PCP-mediated neurotoxicity in the prefrontal and enthorhinal cortices, the striatum and hippocampus was associated with a significant number of neurons exhibiting apoptotic morphology. We found that the total number of apoptotic cells was higher in the brains of 24-month-old rats. Compared to the respective controls the number of apoptotic cells was 3.8-fold greater in the cortex of old rats, followed by the striatum (three-fold), and hippocampus (1.4-fold). Accordingly, we concluded that ageing was accompanied by DNA-damage that was most pronounced in the prefrontal cortical neurones. The most prominent elevation in the degree of apoptosis in the young-treated compared to young-untreated rats was detected in the striatum. Comparison of the number of TUNEL-positive cells in treated-aged versus treated-young rats revealed that in all the examined regions of the brain PCP exerted a stronger apoptotic effect in younger animals.

The connection between absence-like seizures and hypothermia induced by penicillin: possible implication on other animal models of petit mal epilepsy.

In this study we investigated the relationship between penicillin-induced hypothermia and petit mal epilepsy induced by this proconvulsant antibiotic. In order to find a possible dose-dependent relationship, we used two doses: 1500.000 and 1000.000 U/kg b.wt., both known as being sufficient to induce absence-like attacks with subsequent spike and wave discharges (SWD) in electrocorticogram (ECoG). Because of experimental data suggesting penicillin binding to benzodiazepine receptor recognition site, we also studied penicillin-induced changes in body temperature after diazepam pretreatment. Results of this study clearly show that penicillin in doses known to induce petit mal-like epilepsy concomitantly induces statistically significant dose-dependent decrease in body temperature. Pretreatment with diazepam completely prevents both penicillin-induced hypothermia and SWDs. On the other hand, both the diazepam and mixed diazepam + penicillin treatments did not significantly alter body temperature. These results suggest, however, that at least some of the penicillin effects described could be assigned to its binding to the benzodiazepine receptor recognition site at GABA(A) ionophore. This may have an important clinical implication because the inhibitory action of penicillin at the benzodiazepine receptor recognition site could account for the mechanism of penicillin-induced unspecific encephalopathies in humans. The relationship between petit mal epilepsy and hypothermia sheds new light on the action mechanisms of penicillin-induced absence seizures.

[Eponyms and epilepsy (history of Eastern civilizations)]. / Eponimi i epilepsija (istorijat istocnih civilizacija).

The history of eponyms for epilepsy in the lands of the Eastern globe present the portrait of the attitudes of both the laymen and skilled people towards the disease and patient, as well as to the Nature itself. As opposed to the West which during the Middle ages changed its concepts of epilepsy as the organic brain disease for the sublime 'alchemic' position, the people of the East were more prone to consider from the beginning of their civilization till the XIX century that epilepsy is the consequence of the evanescent spiritual and extracorporal forces which by themselves were out of their reach. As compared to the western civilization, the historical resources are, often as a consequence of a linguistic barriers, more scarce-as consequently is the number of eponyms, but are nevertheless picturesque. The medical science from Babylonian period presumed that epileptic manifestations are the consequence of the demonic or ill spiritual actions. There existed an attitude that at the beginning of an epileptic attack the patient was possessed by a demon (the Akkadic, i.e., Babylonian verb "sibtu" denoting epilepsy, had the meaning "to seize" or "to be obsessed"); at the end of the clonic phase the demon departed from the body. Different demons were responsible for different forms of epilepsy such as nocturnal and children epilepsy, absence epilepsy and pure convulsions, simple and complex automatisms, and gelastic epilepsy. Thus, the doctors from the period of Babylon aside from making primordial classification of epilepsies, knew about their clinical picture (prodromal symptoms and aura, Jackson's epilepsy. Todd's paralysis), postictal phenomena and intericatl emotional instability; provocative factors were also known (sleep deprivation, emotions, as well as alcohol, albeit in a negative sense-as a cure for epilepsy). There is no doubt than in the period of Babylon the clinical picture of serial fits and its progress to status epilepticus were clearly recognized and considered as life threatening events. Persian history of epilepsy, except from the 6th century Zoroastrian "Avesta" document, lacks the written or spoken medical heritage untill the 7th century A.D. and the Arabic conquest of the entire Moslem world. On the other hand, Islamic medicine should be freed from the simple prejudice that the Moslem authors were only the translators of Greek medicine; contrary to such a view, their work contains a high degree of individuality. Although Mohammed introduced a lot of novelty into medicine, Khoran and the Sayings do not explicitly refer to epilepsy. Of importance is to notice that Moslem medicine did not have demons in the "repertoire" of direct causes of epilepsy. The causes and the cures of epilepsy were more magic-mystical and occult in nature, which is reminiscent of the European, as well as Serbian Middle age attitudes. Avicenna recognized difference between children and adult epilepsy. He considered insomnia and afternoon siesta as well as intensive sounds and light to be a provocative factors, whereby we see that at least empirically he knew of sleep (deprivation), startle and reflex epilepsy. The XIII century invasion of Mongols brought about the recession in Moslem Medicine; it recovered only in the XVIII century under the strong influence of European medicine handed over to us through Jewish doctors of various nationalities. The story of the China history of epilepsy has its debut approximately in the 8th century B. C. Medical texts from this period name epilepsy "Dian" and "Xian" which meant "the falling sickness" and "convulsions", respectively. Chinese medical terminology often interchangeably used the words "mania", "madness" and "psychosis" for "epilepsy" which, aside from a prominent language barrier, brings additional confusion. Although Chinese documents gave the first description of the grand mal epileptic attack already in the 8th century B. C. (ABSTRACT TRUNCATED)

[Prolonged action of tuftsin in penicillin epilepsy]. / Prolongirovannoe deistvie taftsina v usloviiakh penitsillinovoi épilepsii.

The free behaviour experiments on rats showed during the first day the tuftsin-induced (0.3 mg/kg i. p.) increment of epileptic discharge in all the structures simultaneously. Open field behaviour depended on the sequence of penicillin and tuftsin injections. The rats with tuftsin used after the epileptiformic activity has been developed showed the behaviour analogical to the penicillin-injected animals. The preventive injections of tuftsin resulted in restoration of all behavioural indications by the third day. The optimal corrective effect has been obtained with tuftsin used preventively.

[Effect of penicillin on the synaptic activity of isolated spinal cord motor neurons in the lamprey]. / Vliianie penitsillina na sinapticheskuiu aktivnost' motoneironov izolirovannogo spinnogo mozga minogi.

Penicillin (PCN) has been studied for its effect on the membrane potential (MP) and synaptic activity of lamprey spinal cord motoneurons using intracellular recording in the in vitro spinal cord-notochord preparation. In one group of motoneurons with relative low MP (58.7 +/- 5.2 mV, n = 28) PCN induced depolarization, enhancement and prolongation (up to 80-220%) of the initial amplitude of excitatory postsynaptic potentials (EPSPs) evoked by the stimulation of dorsal roots spinal tracts. If the MPs (in the other group of motoneurons) were high (70.0 +/- 5.7 mV, n = 20) depolarization was not observed and the potentiation of EPSPs did not exceed 25-70% of the initial value. These effects of PCN can be eliminated by a preliminary addition of excitatory or inhibitory amino acid antagonists in the superfusion solution. The obtained results allow suggesting the presence of two different acceptor sites for PCN in membranes of lamprey spinal cord motoneurons.

Penicillin-induced bursting in motoneurones of the frog spinal cord. Elimination by NMDA antagonist.

The effects of penicillin were investigated in lumbar motoneurones of isolated spinal cord preparation of the frog (Rana ridibunda). Spinal root discharges were recorded and single cell activity was studied with intracellular electrodes. Bath application of 500 IU/ml of penicillin G induced in motoneurones prolonged depolarization shifts, followed by repeated transient depolarizations lasting several hours. In all motoneurones studied, this bursting activity was synchronized with discharges recorded from the ventral root. Blockade of N-methyl-D-aspartate (NMDA) receptors by D,L-2-amino-5-phosphonovaleric acid (50-100 microM) completely eliminated the bursting activity. It is suggested that the spinal cord may be an important locus of the anticonvulsant effect of NMDA antagonists.

[Effects of delta sleep-inducing peptide on the intercentral integration during experimental epilepsy]. / Vliianie peptida del'ta-sna na mezhtsentral'nuiu integratsiiu v usloviiakh éksperimental'noi épilepsii.

In free behavior experiments on cats it has been shown, that the intraperitoneal injection of delta-sleep-inducing peptide (100 mg/kg) may change organization of the pathology integration-epileptic discharges did not spread all the structures simultaneously. The slow-waves were registered in central medium of the thalamus and nucl. caudati. The epileptic discharges were registered first in visual and auditory cortex, hippocampus. After that they were observed in the motor cortex, nucl. caudati and centrum medianum of the thalamus.

Effects of sensory-motor cortical lesions on blood-brain permeability in guinea pigs.

Effects of sensory-motor cortical lesions on the function of the blood-brain barrier in distant brain areas are poorly understood. Therefore a brain vascular perfusion method has been used to measure simultaneously the kinetics of entry of two inert polar molecules, D-[14C]mannitol (MW 180) and [3H]polyethylene glycol (PEG; MW 4000), into the parietal cortex, hippocampus, and caudate nucleus in guinea pigs with ipsilateral and contralateral sensory-motor cortical lesions. The graphically determined cerebral capillary unidirectional constant, Kin, indicated a marked increase in blood-to-brain transport of both molecules in all regions studied, the changes being significantly higher after contralateral lesion. The mannitol/PEG cerebrovascular permeability constant ratio, Pman/PPEG, suggested the opening up of channels that permit a flow of fluid carrying substances either with respect to (2 days after ipsilateral lesion) or irrespective of their molecular size, depending on the time after lesion. Amphetamine treatment in the guinea pigs with sensory-motor lesions induced more pronounced blood-brain barrier permeability changes for both molecules in distant brain areas.

The effect of electroconvulsive shock on brain tubulin during development and aging.

Effect of electroconvulsive shock on rat brain tubulin content was studied during maturation and aging. The results show that electroconvulsive shock had no effect on soluble tubulin in different brain structures of young animals (22 days) while the same treatment produced a marked decline in adult (95 days) and aged (490-511 days) animals. The same treatment produced inhibition of 3H-leucine incorporation into tubulin and decrease of 3H-colchicine binding in the proteins of synaptosomes isolated from the centricephalic structures of all the ages examined. Tubulin biosynthesis by free polysomes was not diminished to the extent which could explain the decrease of tubulin level found in the soluble or synaptosomal fraction. Thus, our results suggest that changes in soluble tubulin content in response to electroconvulsive shock could be a reflection of changes in equilibrium: tubulin dimers--microtubules--membrane-bound tubulin.

[Polysensory interaction in the cat posterior ventrolateral thalamic nucleus]. / Polisensornoe vzaimodeistvie v zadnem ventro-lateralsnom iadre talamusa koshki

The neurone activity was studied in the posterior ventrolateral nucleus of the thalamus in acute experiments on unanesthetized cats. About 20% of the neurons studied proved to react to the visual and somatosensory stimulation. By the character of reaction to these stimuli the polymodal neurons could be divided into three groups. In elaboration of the active defense reflex to visual electric skin stimulation there were recorded in the mentioned nucleus the rhythm assimilation reaction with the action of the flickering light and its depression in case a biologically significant stimulus was presented against this background. After section of the optic tract and separation of the hemispheres to the cerebellar level the rhythm assimilation reaction and its depression were revealed in the posterior ventro-lateral nucleus of the thalamus at the side of the section of the optic tract. This fact indicated that the leading canal of the entrance of visual afferentation to this nucleus passed through the stem reticular formation.