BACKGROUND: Methamphetamine (MA) is a highly abused psychostimulant across all age groups including pregnant women. Because developing brain is vulnerable by the action of drugs, or other noxious stimuli, the aim of our study was to examine the effect of early postnatal administration of MA alone or in combination with enriched environment (EE) and/or stress of separate housing, on the levels of serotonin (5HT) in the hippocampus of male rat pups at three stages of adolescence (postnatal day (PND) 28, 35 and 45). MA (5 mg/kg/ml) was administered subcutaneously (sc) to pups (direct administration), or via mothers' milk between PND1 and PND12 (indirect administration). Controls were exposed saline (SA). Pups were exposed to EE and/or to separation from the weaning till the end of the experiment. RESULTS: On PND 28, in sc-treated series, EE significantly increased the muted 5HT in SA pups after separation and restored the pronounced inhibition of 5HT by MA. No beneficial effect of EE was present in pups exposed to combination of MA and separation. 5HT development declined over time; EE, MA and separation had different effects on 5HT relative to adolescence stage. CONCLUSIONS: Present study shows that MA along with environment or housing affect 5HT levels, depending on both the age and the method of application (direct or indirect). These findings extend the knowledge on the effects of MA alone and in combination with different housing conditions on the developing brain and highlight the increased sensitivity to MA during the first few months after birth.

• Klíčová slova
• Adolescence, Enriched environment, Hippocampus, Methamphetamine, Serotonin,
• Publikační typ
• časopisecké články MeSH

Drug addiction and its effect on the behavior and development of children has become a serious problem in our society. Methamphetamine (MA) is one of the most abused psychostimulants in the Czech Republic, and its abuse is rising worldwide. Previous studies have demonstrated the adverse long-term effects of maternal drug abuse on rat offspring. However, the father's contribution as a parent and donor of half of the genetic information is unclear. Previous studies of other psychostimulant drugs indicate that long-term application of MA to adult male rats may induce changes in their reproductive system and lead to changes in rat pup functional and behavioral development. Therefore, the present review aimed to investigate the effect of MA administration on reproductive toxicity and sexual behavior of adult male rats, as well as the impact of paternal MA exposure on behavioral development and locomotor activity in rat offspring.

• MeSH
• chování zvířat MeSH
• dítě MeSH
• dospělí MeSH
• krysa rodu Rattus MeSH
• lidé MeSH
• methamfetamin * škodlivé účinky   MeSH
• pohlavní orgány MeSH
• potkani Wistar MeSH
• sexuální chování MeSH
• stimulanty centrálního nervového systému * farmakologie   MeSH
• zpožděný efekt prenatální expozice * chemicky indukované   MeSH
• zvířata MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• krysa rodu Rattus MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• methamfetamin * MeSH
• stimulanty centrálního nervového systému * 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) is an illicit synthetic psychostimulant drug, and its abuse is growing worldwide. MA has been reported as the primary drug of choice, by drug-abusing women, during pregnancy. Since MA easily crosses the placental barrier, the fetus is exposed to MA in a similar fashion to the mother. This study aimed to evaluate the effect of long-term perinatal stressors and drug exposure on anxiety-like behavior in adult male rats using the open field test (OF) and elevated plus maze (EPM). Dams were divided into three groups according to drug treatment during pregnancy: controls (C), saline-SA [subcutaneous (s.c.), 1 ml/kg], and MA (s.c., 5 mg/kg). Litters were divided into four groups according to postnatal stressors: non-stressed controls (N), maternal separation (S), maternal cold water stress (W), and maternal separation plus maternal cold water stress (SW). Forty-five minutes before testing (in both OF and EPM), one-half of adult male rats received an (s.c.) injection of MA and the other half received an SA injection. Prenatal MA/stress exposure did not affect anxiety-like behavior in adult male rats in both tests. In the OF, an acute MA dose in adulthood increased the time spent in the central disk area, decreased time spent in the corners, and decreased time spent immobile and grooming. Also, postnatal stress increased time spent in the central disk area, decreased time spent in corners, and increased mobility compared to controls. All groups of rats exposed to postnatal stressors spent significantly less time in the closed arms of the EPM compared to controls. Overall, our results indicate that early postnatal stress and a single acute MA administration in adulthood decreases the parameters of anxiety-like behavior in adult male rats regardless of prenatal MA exposure. Moreover, postnatal stress via maternal separation impacts the effect of acute MA administration in adulthood. Long-term postnatal stress may thus result in improved adaptation to subsequent stressful experiences later in life.

• Klíčová slova
• anxiety, elevated plus maze, maternal separation, methamphetamine, open field, postnatal stress, prenatal stress,
• Publikační typ
• časopisecké články 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

Methamphetamine (MA) is an addictive psychostimulant, often abused by drug-addicted women during pregnancy. The offspring of drug-addicted mothers are often exposed to perinatal stressors. The present study examines the effect of perinatal stressors and drug exposure on plasma oxytocin (OXY) levels in female progeny. Rat mothers were divided into three groups according to drug treatment during pregnancy: intact controls (C); saline (SA, s.c., 1 ml/kg); and MA (s.c., 5 mg/kg). Litters were divided into four groups according to postnatal stressors lasting from PD1 to 21: non-stressed controls (N); maternal separation (S); maternal cold-water stress (W); and maternal separation plus cold-water stress (SW). On postnatal day 30, acute MA or SA was administrated 1 h before the rats were sacrificed. Trunk blood was collected and plasma OXY was measured by specific ELISA after extraction. Our results showed that acute MA administration significantly increases plasma OXY levels in juvenile female rats; this effect was observed in prenatally intact rats only. Prenatal exposure of rats to mild stressor of daily SA injection prevented both acute MA-induced OXY stimulation and also stress-induced OXY inhibition. Although postnatal MA and stress exposure exert opposite effects on OXY release in juvenile rats, our data point out the modulatory role of prenatal mild stress in OXY response to postnatal stressors or MA treatment.

• Klíčová slova
• maternal separation, methamphetamine, oxytocin, postnatal stress, prenatal stress,
• Publikační typ
• časopisecké články MeSH

Methamphetamine (MA) is the most abused "hard" illicit drug in the Czech Republic. Drugs abused during pregnancy are not hazardous merely to the mother, but also to developing fetuses. The offspring of drug-addicted mothers are also often exposed to perinatal stressors that may impair brain development of affected progeny. The present study examines the effect of perinatal stressors and drug exposure on cognitive function in male progeny. In the present study, rat mothers were divided into three groups according to drug treatment during pregnancy: controls (C); saline (SA, s.c., 1 ml/kg); MA (s.c., 5 mg/ml/kg). Litters were divided into two groups according to postnatal stressors: non-stressed controls (N); Maternal separation (MS). For evaluation of learning and memory, adult male progeny were tested in the Morris Water Maze (MWM). Our results revealed no significant effects caused by prenatal drug or prenatal stress exposure. On the other hand, chronic postnatal stress, mediated by MS, significantly impaired learning on the Place Navigation test. In addition, MS was associated with changes in search strategies on the Place Navigation, Probe, and Memory Recall tests. Specifically, postnatal stress increased thigmotaxis, indicating less awareness of the hidden platform. In conclusion, the present study provides evidence that exposure to early postnatal stress significantly impairs cognitive functions of male rats, which persists into adulthood.

• Klíčová slova
• learning, maternal separation, memory, methamphetamine, postnatal stress, prenatal stress,
• Publikační typ
• časopisecké články MeSH