Nejvíce citovaný článek - PubMed ID 25669686
Prenatal methamphetamine exposure induces long-lasting alterations in memory and development of NMDA receptors in the hippocampus
Neurotrophins are proteins included in development and functioning of various processed in mammalian organisms. They are important in early development but as well as during adulthood. Brain - derived neurotrophic factor (BDNF) and nerve growth factor (NGF) have been previously linked with many psychiatric disorders such as depression and addiction. Since during postnatal development, brain undergoes various functional and anatomical changes, we included preweaning environment enrichment (EE), since enrichment has been linked with improved function and development of the several brain structure such as hippocampus (HP), in which we monitored these changes. On the other hand, social isolation has been linked with depression and anxiety-like behavior, therefore postweaning social isolation has been added to this model as well and animal were exposed to this condition till adolescence. We examined if all these three factors had impact on BDNF and NGF levels during three phases of adolescence - postnatal days (PDs) 28, 35 and 45. Our results show that EE did not increase BDNF levels neither in control or MA exposed animals and these results are similar for both direct and indirect exposure. On the other side, social separation after weaning did reduce BDNF levels in comparison to standard housing animals but this effect was reversed by direct MA exposure. In terms of NGF, EE environment increased its levels only in indirectly exposed controls and MA animals during late adolescence. On the other hand, social separation increased NGF levels in majority of animals.
- MeSH
- hipokampus MeSH
- krysa rodu Rattus MeSH
- methamfetamin * farmakologie MeSH
- mozek metabolismus MeSH
- mozkový neurotrofický faktor * metabolismus MeSH
- nervový růstový faktor metabolismus MeSH
- zpožděný efekt prenatální expozice * MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- methamfetamin * MeSH
- mozkový neurotrofický faktor * MeSH
- nervový růstový faktor MeSH
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
- Názvy látek
- methamfetamin * MeSH
Attention-deficit/hyperactivity disorder (ADHD) is a mental disorder with a heterogeneous origin with a global incidence that continues to grow. Its causes and pathophysiological mechanisms are not fully understood. It includes a combination of persistent symptoms such as difficulty in concentration, hyperactivity and impulsive behavior. Maternal methamphetamine (MA) abuse is a serious problem worldwide, it can lead to behavioral changes in their offspring that have similarities with behavioral changes seen in children with ADHD. There are several types of ADHD animal models, e.g. genetic models, pharmacologically, chemically and exogenously induced models. One of the exogenously induced ADHD models is the hypoxia-induced model. Our studies, as well as those of others, have demonstrated that maternal MA exposure can lead to abnormalities in the placenta and umbilical cord that result in prenatal hypoxia as well as fetal malnutrition that can result in irreversible changes to experimental animals. Therefore, the aim the present study was to compare the cognitive impairments in MA exposure model with those in established model of ADHD - prenatal hypoxia model, to test whether MA exposure is a valid model of ADHD. Pregnant Wistar rats were divided into four groups based on their gestational exposure to MA: (1) daily subcutaneous injections of MA (5 mg/kg), (2) saline injections at the same time and volume, (3) daily 1-hr hypoxia (10 % O2), and (4) no gestational exposure (controls). Male rat offspring were tested for short-term memory in the Novel Object Recognition Test and the Object Location Test between postnatal days 35 and 40. Also their locomotor activity in both tests was measured. Based on the present results, it seems that prenatal MA exposure is not the best animal model for ADHD since it shows corresponding symptoms only in certain measures. Given our previous results supporting our hypothesis, more experiments are needed to further test possible use of prenatal MA exposure as an animal model of the ADHD.
- MeSH
- chování zvířat * MeSH
- gestační stáří MeSH
- hyperkinetická porucha chemicky indukované patofyziologie psychologie MeSH
- hypoxie plodu komplikace MeSH
- kognice MeSH
- krysa rodu Rattus MeSH
- lokomoce MeSH
- matka - expozice noxám MeSH
- methamfetamin * MeSH
- modely nemocí na zvířatech MeSH
- potkani Wistar MeSH
- těhotenství MeSH
- zpožděný efekt prenatální expozice * MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
- Názvy látek
- methamfetamin * MeSH
Methamphetamine (MA), a psychostimulant, has become a serious problem in recent years. It is one of the most widely abused psychostimulants in the world. In the Czech Republic, ecstasy is the most commonly used non-cannabis drug, followed by hallucinogenic fungi, LSD, MA, cocaine, and finally heroin. The prevalence of the usage of all addictive substances is highest in the age category of 15-34. Approximately 17.2% of registered drug addicts, both male and female, in the Czech Republic use MA as their first-choice drug. This group consists mostly of women who are unemployed and addicted to MA (85%). Almost half of the addicted women switched to MA from other drugs in the course of pregnancy. Psychostimulants such as amphetamine and its synthetic derivate MA induce feelings of calm and happiness by suppressing anxiety and depression. When MA is abused for longer periods, it mimics symptoms of mania and can lead to the development of psychosis. MA is often abused for its anorectic effect, its simple preparation, and compared to heroin and cocaine, its low price. There are significant differences in the susceptibility of users to the stimulant, with reactions to MA fluctuating from person to person. Molecular mechanisms related to the variable response among users might represent an explanation for increased addiction-associated bipolar disorder and psychosis. Currently, there is limited information regarding genetic mechanisms linked to these disorders and the transmission of drug addiction. As such, animal models of drug addiction represent significant sources of information and assets in the research of these issues. The aim of this review is to summarize the mechanism of action of methamphetamine and its effect on pregnant addicted women and their children, including a detailed description of the anatomical structures involved.
- Klíčová slova
- dopamine, drug addiction, hippocampus, methamphetamine, prefrontal cortex, prenatal, serotonin, striatum,
- Publikační typ
- časopisecké články MeSH
- přehledy 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
- Názvy látek
- methamfetamin MeSH
- stimulanty centrálního nervového systému MeSH
Methamphetamine (METH) is a widespread illicit drug. If it is taken by pregnant women, it passes through the placenta and just as it affects the mother, it can impair the development of the offspring. The aim of our study was to identify candidates to investigate for changes in the gene expression in the specific regions of the brain associated with addiction to METH in rats. We examined the various areas of the central nervous system (striatum, hippocampus, prefrontal cortex) for signs of impairment in postnatal day 80 in experimental rats, whose mothers had been administered METH (5 mg/kg/day) during the entire gestation period. Changes in the gene expression at the mRNA level were determined by two techniques, microarray and real-time PCR. Results of two microarray trials were evaluated by LIMMA analysis. The first microarray trial detected either up-regulated or down-regulated expression of 2189 genes in the striatum; the second microarray trial detected either up-regulated or down-regulated expression of 1344 genes in the hippocampus of prenatally METH-exposed rats. We examined the expression of 10 genes using the real-time PCR technique. Differences in the gene expression were counted by the Mann-Whitney U-test. Significant changes were observed in the cocaine- and amphetamine-regulated transcript prepropeptide, tachykinin receptor 3, dopamine receptor D3 gene expression in the striatum regions, in the glucocorticoid nuclear receptor Nr3c1 gene expression in the prefrontal cortex and in the carboxylesterase 2 gene expression in the hippocampus of prenatally METH-exposed rats. The microarray technique also detected up-regulated expression of trace amine-associated receptor 7 h gene in the hippocampus of prenatally METH-exposed rats. We have identified susceptible genes; candidates for the study of an impairment related to methamphetamine addiction in the specific regions of the brain.
- Klíčová slova
- hippocampus, methamphetamine, microarray, prefrontal cortex, prenatal, real-time PCR, receptor, striatum,
- Publikační typ
- časopisecké články MeSH