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Klein A.H.,University of California at Davis | Sawyer C.M.,University of California at Davis | Carstens M.I.,University of California at Davis | Tsagareli M.G.,Beritashvili Institute of Physiology | And 2 more authors.
Behavioural Brain Research | Year: 2010

Menthol is used in analgesic balms and also in foods and oral hygiene products for its fresh cooling sensation. Menthol enhances cooling by interacting with the cold-sensitive thermoTRP channel TRPM8, but its effect on pain is less well understood. We presently used behavioral methods to investigate effects of topical menthol on thermal (hot and cold) pain and innocuous cold and mechanical sensitivity in rats. Menthol dose-dependently increased the latency for noxious heat-evoked withdrawal of the treated hindpaw with a weak mirror-image effect, indicating antinociception. Menthol at the highest concentration (40%) reduced mechanical withdrawal thresholds, with no effect at lower concentrations. Menthol had a biphasic effect on cold avoidance. At high concentrations (10% and 40%) menthol reduced avoidance of colder temperatures (15 °C and 20 °C) compared to 30 °C, while at lower concentrations (0.01-1%) menthol enhanced cold avoidance. In a -5 °C cold plate test, 40% menthol significantly increased the nocifensive response latency (cold hypoalgesia) while lower concentrations were not different from vehicle controls. These results are generally consistent with neurophysiological and human psychophysical data and support TRPM8 as a potential peripheral target of pain modulation. © 2010 Elsevier B.V.


Surguladze S.A.,King's College London | Chkonia E.D.,Tbilisi State Medical University | Kezeli A.R.,Beritashvili Institute of Physiology | Roinishvili M.O.,Beritashvili Institute of Physiology | And 2 more authors.
Schizophrenia Bulletin | Year: 2012

Abnormalities in visual processing have been found consistently in schizophrenia patients, including deficits in early visual processing, perceptual organization, and facial emotion recognition. There is however no consensus as to whether these abnormalities represent heritable illness traits and what their contribution is to psychopathology. Fifty patients with schizophrenia, 61 of their first-degree healthy relatives, and 50 psychiatrically healthy volunteers were tested with regard to facial affect (FA) discrimination and susceptibility to develop the color-contingent illusion [the McCollough Effect (ME)]. Both patients and relatives demonstrated significantly lower accuracy in FA discrimination compared with controls. There was also a significant effect of familiality: Participants from the same families had more similar accuracy scores than those who belonged to different families. Experiments with the ME showed that schizophrenia patients required longer time to develop the illusion than relatives and controls, which indicated poor visual adaptation in schizophrenia. Relatives were marginally slower than controls. There was no significant association between the measures of FA discrimination accuracy and ME in any of the participant groups. Facial emotion discrimination was associated with the degree of interpersonal problems, as measured by the Schizotypal Personality Questionnaire in relatives and healthy volunteers, whereas the ME was associated with the perceptual-cognitive symptoms of schizotypy and positive symptoms of schizophrenia. Our results support the heritability of FA discrimination deficits as a trait and indicate visual adaptation abnormalities in schizophrenia, which are symptom related. © 2010 The Author.


Tsiklauri N.,Beritashvili Institute of Physiology
Georgian medical news | Year: 2010

Several lines of investigations have shown that the microinjection of non-opioid analgesics, non-steroidal anti-inflammatory drugs (NSAIDs) in the midbrain periaqueductal gray matter (PAG) induces antinociception with some effects of tolerance. Our recent findings also have shown the same effects of tolerance in intraperitoneal (i.p.) injections of analgin (metamizol), ketorolac, and xefocam. Moreover, just recently, we have shown that microinjection of three NSAIDs analgin, ketorolac and xefocam into the central nucleus of amygdala produces tolerance to these drugs and cross-tolerance to morphine. The present study was designed to examine whether together with analgin, microinjection of another type of NSAIDs clodifen, ketorolac and xefocam into the PAG and the nucleus raphe magnus (NRM) leads to the development of tolerance in male rats. The experiments were carried out on experimental and control (with saline) white male rats by the models of tail-flick (TF, to the stimulation of focusing light beam) and hot plate (HP, paw withdrawal) tests. For microinjections of NSAIDs stainless steel guide cannula was implanted into the PAG and NRM by the stereotaxic atlas. Latency increase of these reflexes indicated the degree of antinociception. Analysis of variance with post-hoc Dunnet Multiple Comparison Test were used for statistical evaluations. Our study showed that microinjection of NSAIDs into the PAG produced antinociception as revealed by a latency increase in TF and HP compared to the baseline control with saline microinjected into the same nucleus. However, when these drugs microinjection subsequent testing also took place in the following days the antinociceptive effects progressively diminished so that on the 4th and especially the 5th experimental days the TF and HP latencies were similar to the averaged control baseline for rats that received repeated (5 days) injections of only saline. On the 5th day, one hour after of NSAIDs testing, experimental groups of rats received i.p. injections of mu-opioid antagonist naloxone and we did not reveal significant alterations in TP and HP latencies in non-opioid tolerant rats as well as in control animals. Microinjections of NSAIDs into the NRM also produced antinociception as revealed by a latency increase in TF and HP compared to the baseline control of as in intact rats so with saline microinjected ones into the same nucleus. Subsequent NSAIDs microinjections caused progressively less antinociception, so by day 4 there was no effect, similar to saline microinjections (baseline control) for both the TF and the HP tests, except analgin. The later did not show complete tolerance even on the 5th experimental day. Special control experiments showed that post-treatment with naloxone in RVM diminished NSAID-induced antinociception on the first and second experimental days and impeded the development of tolerance to the antinociceptive effect of NSAIDs. Obtained results underscore the strong convergence of antinociceptive mechanisms of opioids and non-opioids, particularly NSAIDs in the PAG-RVM downstream circuit in the acute effect of and the development of tolerance to both types of analgesics. On the other hand, our data confirm the results of other authors that NSAIDs are in close relation with endogenous opioids and the tolerance to these non-opioid drugs probably depends on opioid tolerance.


Dzneladze S.,Beritashvili Institute of Physiology | Tsakadze L.,Beritashvili Institute of Physiology | Leladze M.,Beritashvili Institute of Physiology | Kometiani Z.,Beritashvili Institute of Physiology
Journal of Membrane Biology | Year: 2012

We studied, in the rat brain, the synaptosomal and microsomal membrane fractions of Cl - ion-activated, Mg 2+-dependent ATPase, satisfying the necessary kinetic peculiarities of transport ATPases, by a novel method of kinetic analysis of the multisite enzyme systems: (1) the [Mg-ATP] complex constitutes the substrate of the enzymic reaction; (2) the V = f(Cl -) dependence-reflecting curve is bell-shaped; (3) substrate dependence, V = f(S), curves at a constant concentration of free ligands (Mg f, ATP f, Cl -); (4) as known from the literature, in the process of reaction a phosphorylated intermediate is formed (Gerencser, Crit Rev Biochem Mol Biol 31:303-337, 1996). We report on the Cl -ATPase molecular mechanism and its place in the "P-type ATPase" classification. © 2012 The Author(s).


Chkonia E.,Tbilisi State Medical University | Roinishvili M.,Beritashvili Institute of Physiology | Herzog M.H.,Ecole Polytechnique Federale de Lausanne | Brand A.,Center for Psychiatry and Psychotherapy
Journal of Clinical and Experimental Neuropsychology | Year: 2010

Sustained attention deficits measured by the Continuous Performance Test (CPT) have been reportedly proposed as an endophenotype of schizophrenia. One requirement for an endophenotype is that unaffected first-order relatives must show deteriorated performance compared to healthy controls. We investigated 56 schizophrenic patients, 33 nonaffected first-order relatives, and 36 healthy controls in a degraded and an undegraded version of the CPT of the AX type. Performance of relatives and controls was roughly identical whereas schizophrenic patients performed worse right from the beginning. These results add further evidence that a deficit in the CPT performance is not an endophenotype of schizophrenia in accordance with previous studies. © 2009 Psychology Press, an imprint of the Taylor & Francis Group.


Lazrishvili I.,Beritashvili Institute of Physiology
Georgian medical news | Year: 2011

Manganese is an essential trace element for all living organisms. Though some neurological dysfunction take place during intoxication caused by excessive exposure of this metal. The goal of this research was to elucidate the emotional state, in particular anxiety and fear in three groups of young male rats. Two groups of 30 day old rat pups were given drinking water with MnCl(2)·4H(2)O dissolved in, the doses were 1mg/ml (I group) and 10 mg/ml (II group), and the third group was control animals. Before starting and a day after of termination manganese consumption the animals were tested in the "open field" and "elevated-plus maze". In two month old rat pups compared to one month ones the elevation of anxiety was observed that led to increase of fear. 30 day intoxication of one month old rat pups with both doses of manganese (1 and 10 mg/ml) induces: strengthening of motor and orienting-explorative activity, decrease in the level of anxiety and fear. During the intoxication of animals with above mentioned doses of manganese chloride the dose-dependant effect is not observed.


PubMed | Beritashvili Institute of Physiology
Type: Journal Article | Journal: European journal of pharmacology | Year: 2010

It has recently been shown that antinociceptive tolerance develops by repeated systemic administration of non-steroidal anti-inflammatory drugs (NSAIDs) metamizol and lysine-acetylsalicylate. This is similar to the tolerance observed with opioid-induced analgesia [Vanegas and Tortorici, 2002, Cell and Mol. Neurobiol. 22, 655-661]. In the present study, we investigated the development of tolerance to the analgesic effects of the additional NSAIDs analgine, ketorolac and xefocam in juvenile and adult rats. After injection of each drug, tail-flick latencies were significantly elevated on the first day followed by a progressive decrease in tail-flick latency (i.e., tolerance) over the 5-day period, as well as cross-tolerance to morphine-induced analgesia. Tolerance to the analgesic effect of all three NSAIDs developed more rapidly in juvenile compared to adult rats. Pretreatment with naloxone completely prevented the analgesic effects of these drugs in tail-flick and hot plate tests for both juvenile and adult rats. Moreover, each NSAID exhibited cross-tolerance when tolerance to morphine had been induced by systemic morphine delivered repeatedly over 5-day period in both age groups. Our data confirm other recent findings that tolerance to the analgesic action of NSAIDs may depend on an opiate-mediated mechanism.


PubMed | Beritashvili Institute of Physiology
Type: Journal Article | Journal: Georgian medical news | Year: 2011

Manganese is an essential trace element for all living organisms. Though some neurological dysfunction take place during intoxication caused by excessive exposure of this metal. The goal of this research was to elucidate the emotional state, in particular anxiety and fear in three groups of young male rats. Two groups of 30 day old rat pups were given drinking water with MnCl(2)4H(2)O dissolved in, the doses were 1mg/ml (I group) and 10 mg/ml (II group), and the third group was control animals. Before starting and a day after of termination manganese consumption the animals were tested in the open field and elevated-plus maze. In two month old rat pups compared to one month ones the elevation of anxiety was observed that led to increase of fear. 30 day intoxication of one month old rat pups with both doses of manganese (1 and 10 mg/ml) induces: strengthening of motor and orienting-explorative activity, decrease in the level of anxiety and fear. During the intoxication of animals with above mentioned doses of manganese chloride the dose-dependant effect is not observed.


PubMed | Beritashvili Institute of Physiology
Type: Journal Article | Journal: The Journal of membrane biology | Year: 2012

We studied, in the rat brain, the synaptosomal and microsomal membrane fractions of Cl ion-activated, Mg-dependent ATPase, satisfying the necessary kinetic peculiarities of transport ATPases, by a novel method of kinetic analysis of the multisite enzyme systems: (1) the [Mg-ATP] complex constitutes the substrate of the enzymic reaction; (2) the V = f(Cl) dependence-reflecting curve is bell-shaped; (3) substrate dependence, V = f(S), curves at a constant concentration of free ligands (Mg(f), ATP(f), Cl); (4) as known from the literature, in the process of reaction a phosphorylated intermediate is formed (Gerencser, Crit Rev Biochem Mol Biol 31:303-337, 1996). We report on the Cl-ATPase molecular mechanism and its place in the P-type ATPase classification.

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