There is growing evidence that methamphetamine use during pregnancy may produce detrimental cardiovascular effects in the adult offspring. Prior work demonstrated that chronic methamphetamine exposure throughout the gestational period causes adult female offspring to become hypersensitive to myocardial ischemic injury. The goal of the present study was to determine whether this methamphetamine-induced effect occurs early or late in the gestational period. Pregnant female rats were divided into 4 experimental groups. Groups 1 and 2 received subcutaneous injections of saline (group 1) or methamphetamine (5 mg/kg) (group 2) throughout the gestational period. Group 3 received methamphetamine injections on days 1-11 and saline on days 12-22, and group 4 received saline on days 1-11 and methamphetamine on days 12-22. Hearts were isolated from adult (8 weeks) female offspring and subjected to 30 min ischemia and 2 hours reperfusion on a Langendorff isolated heart apparatus. Contractile function was measured via an intraventricular balloon, and infarct size was measured by triphenyltetrazolium chloride staining. Infarcts were significantly larger in methamphetamine exposed offspring regardless of whether they had been exposed to methamphetamine during the first half or the second half of the gestational period. Prenatal exposure to methamphetamine had no effect on preischemic contractile function or postischemic recovery of contractile function. These data indicate that methamphetamine use during either the first half or second half of pregnancy increases susceptibility to myocardial infarction in adult female offspring. These data provide further evidence that prenatal exposure to methamphetamine may increase the risk of developing cardiovascular diseases during adulthood.
- MeSH
- infarkt myokardu * MeSH
- krysa rodu rattus MeSH
- lidé MeSH
- methamfetamin * toxicita MeSH
- poranění srdce * MeSH
- potkani Sprague-Dawley MeSH
- srdce MeSH
- těhotenství MeSH
- zpožděný efekt prenatální expozice * chemicky indukované MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
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
Methamphetamine (MA), as massively abused psychoactive stimulant, has been associated with many neurological diseases. It has various potent and neurotoxic properties. There are many mechanisms of action that contribute to its neurotoxic and degenerative effects, including excessive neurotransmitter (NEU) release, blockage of NEU uptake transporters, degeneration of NEU receptors, process of oxidative stress etc. MA intoxication is caused by blood-brain barrier disruption resulted from MA-induced oxidation stress. In our laboratory we constantly work on animal research of MA. Our current interest is to investigate processes of MA-induced alteration in neurotransmission, especially during development of laboratory rat. This review will describe current understanding in role of NEUs, which are affected by MA-induced neurotoxicity caused by altering the action of NEUs in the central nervous system (CNS). It also briefly brings information about NEUs development in critical periods of development.
- MeSH
- centrální nervový systém účinky léků růst a vývoj metabolismus MeSH
- chování zvířat účinky léků MeSH
- krysa rodu rattus MeSH
- lidé MeSH
- methamfetamin toxicita MeSH
- nervový přenos účinky léků MeSH
- neurogeneze účinky léků MeSH
- neurotoxické syndromy etiologie metabolismus patologie MeSH
- neurotransmiterové látky toxicita MeSH
- stimulanty centrálního nervového systému toxicita MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Závěrečná zpráva o řešení grantu Agentury pro zdravotnický výzkum MZ ČR
Nestr.
Závislost na metamfetaminu a opioidech je u těhotných žen významným veřejnozdravotním problémem i v mezinárodním měřítku, spojeným s vysokými zdravotními a sociálními dopady na ženy a děti. Studie se zaměří na neonatální a dlouhodobé následky u dětí vystavených působení nelegálních drog nebo opiátové substituční léčbě (OMT) během fetálního života u rozsáhlé kohorty českých těhotných žen. Design studie bude kohortová retrospektnivní studie, jako zdroje dat budou využity národní zdravotní registry, resp. údaje z 5 národních zdravotních registrů a 2 národních informačních systémů, které budou propojeny pomocí rodného čísla. Studie je unikátní extenzivním využitím národních zdravotních registrů pro sledování dlouhodobých zdravotních následků u dětí exponovaných prenatálně drogám a OMT svých matek. Studie přinese doporučení ke zkvalitnění národního registru reprodukčního zdraví a péče o těhotné uživatelky drog a jejich děti.; Methamphetamine- and opioid-dependence in pregnant women is a major public health issue internationally, associated with high health and social burden in women and their children. Study focuses on neonatal and long-term outcomes in children exposed to illegal drugs or opioid maintenance treatment (OST) during fetal life in a large Czech pregnancy cohort. Design will be retrospective cohort utilising national health registers,specifically 5 national health registries and 2 national information systems linking data by the unique civil registration number. The study is unique by its extensive use of national health registers for research of long-term outcomes in children prenatally exposed to drugs and OMT in their mothrs. Study will bring recommendations for inovation of national register of reproductive health and for the care of pregnant drug users and their children.
- MeSH
- dospělí MeSH
- heroin toxicita MeSH
- kohortové studie MeSH
- kojenec MeSH
- lidé MeSH
- methamfetamin toxicita MeSH
- novorozenec MeSH
- novorozenecký abstinenční syndrom MeSH
- opiátová substituční terapie škodlivé účinky MeSH
- poruchy spojené s užíváním amfetaminu MeSH
- předškolní dítě MeSH
- průřezové studie MeSH
- registrace MeSH
- těhotné ženy MeSH
- závislost na heroinu MeSH
- životní styl MeSH
- Check Tag
- dospělí MeSH
- kojenec MeSH
- lidé MeSH
- novorozenec MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Konspekt
- Patologie. Klinická medicína
- NLK Obory
- toxikologie
- perinatologie a neonatologie
- adiktologie
- NLK Publikační typ
- závěrečné zprávy o řešení grantu AZV MZ ČR
Methamphetamine, mainly consumed as an illicit drug, is a potent addictive psychostimulant that has been detected in surface water at concentrations ranging from nanograms to micrograms per litre, especially in Middle and East Europe. The aim of this study was to expose brown trout (Salmo trutta fario) to environmental (1 μg L-1) and higher (50 μg L-1) concentrations of methamphetamine for 35 days with a four-day depuration phase to assess the possible negative effects on fish health. Degenerative liver and heart alterations, similar to those described in mammals, were observed at both concentrations, although at different intensities. Apoptotic changes in hepatocytes, revealed by activated caspase-3, were found in exposed fish. The parent compound and a metabolite (amphetamine) were detected in fish tissues in both concentration groups, in the order of kidney > liver > brain > muscle > plasma. Bioconcentration factors ranged from 0.13 to 80. A therapeutic plasma concentration was reached for both compounds in the high-concentration treatment. This study indicates that chronic environmental concentrations of methamphetamine can lead to health issues in aquatic organisms.
- MeSH
- chemické látky znečišťující vodu toxicita MeSH
- játra metabolismus MeSH
- ledviny patologie MeSH
- methamfetamin toxicita MeSH
- pstruh metabolismus fyziologie MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Evropa MeSH
Methamphetamine (MA), as a psychostimulant drug that crosses the placental barrier, may disrupt the development of social play. The present study aims to examine the effect of prenatal MA (5 mg/kg) exposure during the first (gestational day (GD) 1-11) or second (GD 12-22) halves of prenatal development of rats on social play behavior. To investigate an acute effect of MA on social play in adulthood, juvenile rats were exposed to a dose of 1 mg/kg MA or saline on the test day and tested for social play for 15 min. Prenatal exposure to MA during GD 1-11 increased social play behavior during 5-10 min interval of the test in males but not females. Prenatal MA during GD 12-22 did not influence social play in males nor females. However, social play occurred to a greater extent in GD 12-22 groups compared with GD 1-11. Acute exposure to MA eliminated playful behavior in all groups and decreased social exploration in GD 1-11. Our results suggest that manipulation of prenatal development during the first half of the gestational period has a greater impact on social play behavior than during the second half.
- MeSH
- gestační stáří MeSH
- hra a hračky psychologie MeSH
- krysa rodu rattus MeSH
- methamfetamin toxicita MeSH
- novorozená zvířata MeSH
- potkani Wistar MeSH
- sociální chování * MeSH
- stimulanty centrálního nervového systému toxicita MeSH
- těhotenství MeSH
- zpožděný efekt prenatální expozice chemicky indukované psychologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Methamphetamine (METH), a central nervous system stimulant used as a recreational drug, is frequently found in surface waters at potentially harmful concentrations. To determine effects of long-term exposure to environmentally relevant levels on nontarget organisms, we analysed cardiac and locomotor responses of signal crayfish Pacifastacus leniusculus to acute stress during a 21-day exposure to METH at 1 μg L-1 followed by 14 days depuration. Heart rate and locomotion were recorded over a period of 30 min before and 30 min after exposure to haemolymph of an injured conspecific four times during METH exposure and four times during the depuration phase. Methamphetamine-exposed crayfish showed a weaker cardiac response to stress than was observed in controls during both exposure and depuration phases. Similarly, methamphetamine-exposed crayfish, during METH exposure, showed lower locomotor reaction poststressor application in contrast to controls. Results indicate biological alterations in crayfish exposed to METH at low concentration level, potentially resulting in a shift in interactions among organisms in natural environment.
The hyperpolarization-activated cyclic-nucleotide-gated non-selective cation (HCN) channels play a potential role in the neurological basis underlying drug addiction. However, little is known about the role of HCN channels in methamphetamine (METH) abuse. In the present study, we examined the changes in working memory functions of METH re-exposed mice through Morris water maze test, and investigated the protein expression of HCN1 channels and potential mechanisms underlying the modulation of HCN channels by Western blotting analysis. Mice were injected with METH (1 mg/kg, i.p.) once per day for 6 consecutive days. After 5 days without METH, mice were re-exposed to METH at the same concentration. We found that METH re-exposure caused an enhancement of working memory, and a decrease in the HCN1 channels protein expression in both hippocampus and prefrontal cortex. The phosphorylated extracellular regulated protein kinase 1/2 (p-ERK1/2), an important regulator of HCN channels, was also obviously reduced in hippocampus and prefrontal cortex of mice with METH re-exposure. Meanwhile, acute METH exposure did not affect the working memory function and the protein expressions of HCN1 channels and p-ERK1/2. Overall, our data firstly showed the aberrant protein expression of HCN1 channels in METH re-exposed mice with enhanced working memory, which was probably related to the down-regulation of p-ERK1/2 protein expression.
- MeSH
- down regulace účinky léků fyziologie MeSH
- draslíkové kanály biosyntéza MeSH
- hipokampus účinky léků metabolismus MeSH
- hyperpolarizační iontové kanály řízené cyklickými nukleotidy antagonisté a inhibitory biosyntéza MeSH
- krátkodobá paměť účinky léků fyziologie MeSH
- lokomoce účinky léků fyziologie MeSH
- methamfetamin aplikace a dávkování toxicita MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- náhodné rozdělení MeSH
- prefrontální mozková kůra účinky léků metabolismus MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Methamphetamine (METH) abuse is known to increase the risk of Parkinson's disease (PD) due to its dopaminergic neurotoxicity. This is the rationale for the METH model of PD developed by toxic METH dosing (10 mg/kg four times every 2 h) which features robust neurodegeneration and typical motor impairment in mice. In this study, we used diffusion kurtosis imaging to reveal microstructural brain changes caused by METH-induced neurodegeneration. The METH-treated mice and saline-treated controls underwent diffusion kurtosis imaging scanning using the Bruker Avance 9.4 Tesla MRI system at two time-points: 5 days and 1 month to capture both early and late changes induced by METH. At 5 days, we found a decrease in kurtosis in substantia nigra, striatum and sensorimotor cortex, which is likely to indicate loss of DAergic neurons. At 1 month, we found an increase of kurtosis in striatum and sensorimotor cortex and hippocampus, which may reflect certain recovery processes. Furthermore, we performed tract-based spatial statistics analysis in the white matter and at 1 month, we observed increased kurtosis in ventral nucleus of the lateral lemniscus and some of the lateral thalamic nuclei. No changes were present at the early stage. This study confirms the ability of diffusion kurtosis imaging to detect microstructural pathological processes in both grey and white matter in the METH model of PD. The exact mechanisms underlying the kurtosis changes remain to be elucidated but kurtosis seems to be a valuable biomarker for tracking microstructural brain changes in PD and potentially other neurodegenerative disorders.
- MeSH
- chování zvířat účinky léků MeSH
- difuzní magnetická rezonance MeSH
- dopaminové látky toxicita MeSH
- methamfetamin toxicita MeSH
- modely nemocí na zvířatech MeSH
- mozek diagnostické zobrazování účinky léků patologie MeSH
- myši inbrední C57BL MeSH
- Parkinsonova nemoc sekundární diagnostické zobrazování patologie MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Pharmaceutically active compounds are major contaminants of aquatic environments that show direct and indirect effects on aquatic organisms even at low concentrations. The aim of this study was to assess the effects of the illicit drug methamphetamine and the antidepressant sertraline on clonal marbled crayfish Procambarus virginalis. Crayfish exposed to the environmentally relevant concentrations of methamphetamine of ∼1 μg L-1 did not exhibit significant differences from unexposed controls in distance moved, velocity, and activity level with or without available shelter. Sertraline-exposed (∼1 μg L-1) crayfish were significantly more active, regardless of available shelter, and moved greater distances when shelter was available, compared to control crayfish. Crayfish exposed to methamphetamine and sertraline spent significantly more time outside the shelters compared to controls. Sertraline-exposed crayfish spawned more frequently and showed higher mortality than controls. The results suggest that the low environmental concentrations of the tested compounds could alter the behavior and life history traits of crayfish, resulting in higher reproductive effort and mortality.
- MeSH
- bezobratlí MeSH
- chemické látky znečišťující vodu toxicita MeSH
- chování zvířat účinky léků MeSH
- methamfetamin toxicita MeSH
- sertralin toxicita MeSH
- severní raci účinky léků růst a vývoj MeSH
- stadia vývoje účinky léků MeSH
- vodní organismy účinky léků růst a vývoj MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH