Methamphetamine (MA) is one of the most abused psychostimulants in the Czech Republic and worldwide. Previous studies have demonstrated the adverse effects of maternal drug abuse. However, the father's contribution as a parent and donor of the half genetic information is unclear. The present study aimed to examine the effect of paternal MA exposure on behavioral development and locomotor activity in rat offspring. MA was administrated subcutaneously for 30 days at a dose of 5 mg/kg to adult male rats. The impact of paternal MA exposure on rat pups was investigated using behavioral tests during development and locomotor activity tests in adulthood. Prior to testing, adult offspring were exposed to an acute challenge dose of MA (1 mg/kg) to examine the possible sensitizing effect of the paternal treatment. Our results found no significant differences in behavioral development or locomotor activity in adulthood of offspring linked to paternal MA application. These results differ from the effects induced by maternal MA application. Further, our results demonstrated a significant increase in locomotor activity on the Laboras test after acute MA application. When comparing sex differences, females showed more activity than males in adulthood, whereas males were more active during development.

• MeSH
• chování zvířat účinky léků   MeSH
• krysa rodu Rattus MeSH
• lokomoce účinky léků   MeSH
• methamfetamin toxicita   MeSH
• metoda rotující tyčky MeSH
• otec - expozice noxám * MeSH
• pohlavní dimorfismus MeSH
• polohový reflex účinky léků   MeSH
• potkani Wistar MeSH
• senzorimotorický kortex účinky léků   růst a vývoj   MeSH
• sexuální faktory MeSH
• stimulanty centrálního nervového systému toxicita   MeSH
• věkové faktory MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH
• Názvy látek
• methamfetamin MeSH
• stimulanty centrálního nervového systému MeSH

BACKGROUND: Olanzapine is a frequently used atypical antipsychotic drug known to exert structural brain alterations in animals. This study investigated whether chronic olanzapine exposure alters regional blood brain perfusion assessed by Arterial Spin Labelling (ASL) magnetic resonance imaging (MRI) in a validated model of olanzapine-induced metabolic disturbances. An effect of acute olanzapine exposure on brain perfusion was also assessed for comparison. METHODS: Adult Sprague-Dawley female rats were treated by intramuscular depot olanzapine injections (100 mg/kg every 14 days) or vehicle for 8 weeks. ASL scanning was performed on a 9.4 T Bruker BioSpec 94/30USR scanner under isoflurane anesthesia. Serum samples were used to assay leptin and TNF-α level while brains were sliced for histology. Another group received only one non-depot intraperitoneal dose of olanzapine (7 mg/kg) during MRI scanning, thus exposing its acute effect on brain perfusion. RESULTS: Both acute and chronic dosing of olanzapine resulted in decreased perfusion in the sensorimotor cortex, while no effect was observed in the piriform cortex or hippocampus. Furthermore, in the chronically treated group decreased cortex volume was observed. Chronic olanzapine dosing led to increased body weight, adipose tissue mass and leptin level, confirming its expected metabolic effects. CONCLUSION: This study demonstrates region-specific decreases in blood perfusion associated with olanzapine exposure present already after the first dose. These findings extend our understanding of olanzapine-induced functional and structural brain changes.

• Klíčová slova
• Arterial spin labelling, Cortex, Leptin, Olanzapine, Sprague-Dawley rats,
• MeSH
• antipsychotika aplikace a dávkování   škodlivé účinky   MeSH
• magnetická rezonanční tomografie MeSH
• mozkový krevní oběh účinky léků   MeSH
• olanzapin aplikace a dávkování   škodlivé účinky   MeSH
• potkani Sprague-Dawley MeSH
• rozvrh dávkování léků MeSH
• senzorimotorický kortex krevní zásobení   diagnostické zobrazování   účinky léků   MeSH
• velikost orgánu účinky léků   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antipsychotika MeSH
• olanzapin MeSH

Clinical studies consistently report structural impairments (i.e.: ventricular enlargement, decreased volume of anterior cingulate cortex or hippocampus) and functional abnormalities including changes in regional cerebral blood flow in individuals suffering from schizophrenia, which can be evaluated by magnetic resonance imaging (MRI) techniques. The aim of this study was to assess cerebral blood perfusion in several schizophrenia-related brain regions using Arterial Spin Labelling MRI (ASL MRI, 9.4 T Bruker BioSpec 94/30USR scanner) in rats. In this study, prenatal exposure to methylazoxymethanol acetate (MAM, 22 mg/kg) at gestational day (GD) 17 and the perinatal treatment with Δ-9-tetrahydrocannabinol (THC, 5 mg/kg) from GD15 to postnatal day 9 elicited behavioral deficits consistent with schizophrenia-like phenotype, which is in agreement with the neurodevelopmental hypothesis of schizophrenia. In MAM exposed rats a significant enlargement of lateral ventricles and perfusion changes (i.e.: increased blood perfusion in the circle of Willis and sensorimotor cortex and decreased perfusion in hippocampus) were detected. On the other hand, the THC perinatally exposed rats did not show differences in the cerebral blood perfusion in any region of interest. These results suggest that although both pre/perinatal insults showed some of the schizophrenia-like deficits, these are not strictly related to distinct hemodynamic features.

• MeSH
• circulus arteriosus Willisi diagnostické zobrazování   účinky léků   embryologie   MeSH
• hipokampus krevní zásobení   diagnostické zobrazování   účinky léků   embryologie   MeSH
• krysa rodu Rattus MeSH
• lidé MeSH
• magnetická rezonanční angiografie metody   MeSH
• methylazoxymethanolacetát toxicita   MeSH
• modely nemocí na zvířatech MeSH
• mozkový krevní oběh účinky léků   MeSH
• neurogeneze účinky léků   MeSH
• schizofrenie chemicky indukované   diagnóza   MeSH
• senzorimotorický kortex krevní zásobení   diagnostické zobrazování   účinky léků   embryologie   MeSH
• techniky pozorování chování MeSH
• těhotenství MeSH
• tetrahydrokanabinol toxicita   MeSH
• zpožděný efekt prenatální expozice chemicky indukované   diagnostické zobrazování   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• lidé MeSH
• mužské pohlaví MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• methylazoxymethanolacetát MeSH
• tetrahydrokanabinol MeSH

Botulinum toxin type A (BoNT) is considered an effective therapeutic option in cervical dystonia (CD). The pathophysiology of CD and other focal dystonias has not yet been fully explained. Results from neurophysiological and imaging studies suggest a significant involvement of the basal ganglia and thalamus, and functional abnormalities in premotor and primary sensorimotor cortical areas are considered a crucial factor in the development of focal dystonias. Twelve BoNT-naïve patients with CD were examined with functional MRI during a skilled hand motor task; the examination was repeated 4 weeks after the first BoNT injection to the dystonic neck muscles. Twelve age- and gender-matched healthy controls were examined using the same functional MRI paradigm without BoNT injection. In BoNT-naïve patients with CD, BoNT treatment was associated with a significant increase of activation in finger movement-induced fMRI activation of several brain areas, especially in the bilateral primary and secondary somatosensory cortex, bilateral superior and inferior parietal lobule, bilateral SMA and premotor cortex, predominantly contralateral primary motor cortex, bilateral anterior cingulate cortex, ipsilateral thalamus, insula, putamen, and in the central part of cerebellum, close to the vermis. The results of the study support observations that the BoNT effect may have a correlate in the central nervous system level, and this effect may not be limited to cortical and subcortical representations of the treated muscles. The results show that abnormalities in sensorimotor activation extend beyond circuits controlling the affected body parts in CD even the first BoNT injection is associated with changes in sensorimotor activation. The differences in activation between patients with CD after treatment and healthy controls at baseline were no longer present.

• Klíčová slova
• Botulinum toxin, Brain plasticity, Cervical dystonia, Functional MRI,
• MeSH
• aferentní nervové dráhy diagnostické zobrazování   účinky léků   MeSH
• botulotoxiny typu A terapeutické užití   MeSH
• dospělí MeSH
• kyslík krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie metody   MeSH
• neparametrická statistika MeSH
• nervosvalové látky terapeutické užití   MeSH
• počítačové zpracování obrazu MeSH
• psychomotorický výkon účinky léků   MeSH
• senioři MeSH
• senzorimotorický kortex diagnostické zobrazování   účinky léků   MeSH
• tortikolis * diagnostické zobrazování   farmakoterapie   patofyziologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• botulotoxiny typu A MeSH
• kyslík MeSH
• nervosvalové látky MeSH

Ro 25-6981 maleate is a highly selective and activity-dependent antagonist of NMDA ionotropic glutamate receptors containing NR2B subunit (NR2B/NMDARs). The aim of our study was to investigate the influence of Ro 25-6981 administration in developing rats on physiological (single and paired pulse cortical interhemispheric evoked potentials) and epileptic brain activity (cortical afterdischarges (ADs)). Electrophysiological experiments were performed in animals with epidurally implanted electrodes at postnatal days (P) P12, P18, and P25. The drug was injected intraperitoneally at a dose of 1 or 3mg/kg. Control animals were injected with saline (1ml/kg). Single interhemispheric responses were evoked with 0.5-ms biphasic pulses with intensities increasing from 0.4 to 5mA, paired-pulse responses were elicited by twofold threshold intensity. The ADs were elicited by series of 15-s of 1-ms pulses at 8-Hz frequency. Firstly, six stimulations with stable suprathreshold intensity repeated at 30-min intervals were used to determine the time course of Ro 25-6981 effects against ADs in P12 animals. Secondly, similar experiment was performed in all age groups of animals but with 20-min intervals as well as a further experiment using stimulations with stepwise intensities increasing at 10-min intervals from 0.2 to 15 mA. Pretreatment with the 3-mg/kg (but not the lower) dose of Ro 25-9681 decreased significantly the amplitude of single responses evoked with higher stimulation intensities in P12 and P18 animals. Both doses affected responses in P25 animals, only the 1-mg/kg dose was more efficacious than the 3-mg/kg one. Paired pulse responses were not affected by either dose of Ro 25-6981 in any age group. Ro 25-9681 clearly influenced the duration of ADs only in P12 animals. The 1-mg/kg dose did not change the duration of ADs whereas the 3-mg/kg dose suppressed progressive prolongation of ADs with repeated stimulations. This effect was seen even 110-min after the drug injection. The modification of ADs, i.e. stimulations with stepwise increasing intensities (10 min intervals) was used to demonstrate possible dependence on activity. The Ro 25-6981 was administered immediately after the 4-mA stimulation (i.e. when rats experienced six ADs on the average). The 3-mg/kg dose resulted in shorter ADs after high stimulation intensities in P12. There were no significant effects in older animals, only a tendency to ADs shortening was observed in P25 rats. In conclusion, our results indicate that Ro 25-6981 as a selective antagonist of NR2B/NMDARs exhibit age- and activation-dependent anticonvulsant action at early postnatal development. In contrast, the influence of Ro 25-6981 on physiological excitability induced by single pulse stimulation of sensorimotor cortex does not depend on age. This compound may thus represent a useful antiepileptic agent in immature brain since its action against ADs prolongation can be observed even 110 min after the single administration of the drug.

• Klíčová slova
• Cortical epileptic afterdischarges, Cortical responses, NMDA receptors, NR2B subunit antagonist, Postnatal development, Rat,
• MeSH
• antikonvulziva aplikace a dávkování   MeSH
• elektrická stimulace MeSH
• fenoly aplikace a dávkování   MeSH
• krysa rodu Rattus MeSH
• membránové potenciály účinky léků   MeSH
• piperidiny aplikace a dávkování   MeSH
• potkani Wistar MeSH
• receptory N-methyl-D-aspartátu antagonisté a inhibitory   MeSH
• senzorimotorický kortex účinky léků   patofyziologie   MeSH
• věkové faktory MeSH
• záchvaty farmakoterapie   patofyziologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antikonvulziva MeSH
• fenoly MeSH
• NR2B NMDA receptor MeSH Prohlížeč
• piperidiny MeSH
• receptory N-methyl-D-aspartátu MeSH
• Ro 25-6981 MeSH Prohlížeč

BACKGROUND AND PURPOSE: Botulinum toxin (BoNT) treatment relieves focal arm spasticity after stroke, likely acting at several hierarchical levels of the motor system. The central correlate of BoNT-induced spasticity relief may be detected using repeated functional MRI (fMRI) during motor task. METHODS: Five patients (4 males, 1 female, mean age 67 years) with hemiparesis and distal arm spasticity after chronic ischemic stroke were studied. FMRI was performed while moving the paretic hand in three sessions: before and 4 and 11 weeks after BoNT treatment. RESULTS: Arm spasticity significantly decreased following BoNT treatment across the group (mean modified Ashworth scale change .6). FMRI prior to BoNT treatment showed extensive bilateral active networks, whereas post-BoNT activation was limited to midline and contralateral sensorimotor cortices, and the third examination, when the toxin effect has worn off, again showed extensive activation similar to pre-BoNT examination. Post-BoNT session 2 compared to sessions 1 and 3 demonstrated a significantly less activation in contralateral frontoparietal areas including inferior frontal, postcentral, and middle frontal gyri as well as transient crossed cerebellar activation. CONCLUSION: Relief of post-stroke arm spasticity may be associated with changes at several hierarchical levels of the cortical sensorimotor system, including the prefrontal cortex.

• Klíčová slova
• Stroke, arm spasticity, botulinum toxin, finger movement, functional magnetic resonance imaging,
• MeSH
• botulotoxiny typu A terapeutické užití   MeSH
• cévní mozková příhoda komplikace   farmakoterapie   patofyziologie   MeSH
• evokované potenciály * MeSH
• lidé středního věku MeSH
• lidé MeSH
• nervosvalové látky terapeutické užití   MeSH
• paže MeSH
• pohyb MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• senzorimotorický kortex účinky léků   patofyziologie   MeSH
• svalová spasticita farmakoterapie   etiologie   patofyziologie   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• práce podpořená grantem MeSH
• Názvy látek
• botulotoxiny typu A MeSH
• nervosvalové látky MeSH