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

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

The present study was aimed at evaluating cognitive changes following neonatal methamphetamine exposure in combination with repeated treatment in adulthood of female Wistar rats. Pregnant dams and their pups were used in this study. One half of the offspring were treated indirectly via the breast milk of injected mothers, and the other half of pups were treated directly by methamphetamine injection. In the group with indirect exposure, mothers received methamphetamine (5 mg/ml/kg) or saline (1 ml/kg) between postnatal days (PD) 1-11. In the group with direct exposure, none of the mothers were treated. Instead, progeny were either: (1) treated with injected methamphetamine (5 mg/ml/kg); or (2) served as controls and received sham injections (no saline, just a needle stick) on PD 1-11. Learning ability and memory consolidation were tested on PD 70-90 in the Morris Water Maze (MWM) using three tests: Place Navigation Test, Probe Test, and Memory Recall Test. Adult female progeny were injected daily, after completion of the last trial of MWM tests, with saline or methamphetamine (1 mg/ml/kg). The effects of indirect/direct neonatal methamphetamine exposure combined with acute adult methamphetamine treatment on cognitive functions in female rats were compared. Statistical analyses showed that neonatal drug exposure worsened spatial learning and the ability to remember the position of a hidden platform. The study also demonstrated that direct methamphetamine exposure has a more significant impact on learning and memory than indirect exposure. The acute dose of the drug did not produce any changes in cognitive ability. Analyses of search strategies (thigmotaxis, scanning) used by females during the Place Navigation Test and Memory Recall Test confirmed all these results. Results from the present study suggested extensive deficits in learning skills and memory of female rats that may be linked to the negative impact of neonatal methamphetamine exposure.

• Klíčová slova
• Morris Water Maze (MWM), Wistar rat, methamphetamine, neonatal exposure, strategies,
• Publikační typ
• časopisecké články 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

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

Methamphetamine (MA) is the most commonly used psychostimulant drug, the chronic abuse of which leads to neurodegenerative changes in the brain. The global use of MA is increasing, including in pregnant women. Since MA can cross both placental and haematoencephalic barriers and is also present in maternal milk, children of chronically abused mothers are exposed prenatally as well as postnatally. Women seem to be more vulnerable to some aspects of MA abuse than men. MA is thought to exert its effects among others via direct interactions with dopamine transporters (DATs) in the brain tissue. Sexual dimorphism of the DAT system could be a base of sex-dependent actions of MA observed in behavioural and neurochemical studies. Possible sex differences in the DATs of preadolescent offspring exposed to MA prenatally and/or postnatally have not yet been evaluated. We examined the striatal synaptosomal DATs (the activity and density of surface expressed DATs and total DAT expression) in preadolescent male and female Wistar rats (31-35-day old animals) exposed prenatally and/or postnatally to MA (daily 5 mg/kg, s.c. to mothers during pregnancy and lactation). To distinguish between specific and nonspecific effects of MA on DATs, we also evaluated the in vitro effects of lipophilic MA on the fluidity of striatal membranes isolated from preadolescent and young adult rats of both sexes. We observed similar changes in the DATs of preadolescent rats exposed prenatally or postnatally (MA-mediated drop in the reserve pool but no alterations in surface-expressed DATs). However, prenatal exposure evoked significant changes in males and postnatal exposure in females. A significant decrease in the activity of surface-expressed DATs was found only in postnatally exposed females sensitized to MA via prenatal exposure. MA applied in vitro increased the fluidity of striatal membranes of preadolescent female but not male rats. In summary, DATs of preadolescent males are more sensitive to prenatal MA exposure via changes in the reserve pool and those of preadolescent females to postnatal MA exposure via the same mechanism. The combination of prenatal and postnatal MA exposure increases the risk of dopaminergic deficits via alterations in the activity of surface-expressed DATs especially in preadolescent females. MA-mediated changes in DATs of preadolescent females could be still enhanced via nonspecific disordering actions of MA on striatal membranes.

• Klíčová slova
• Dopamine transporter, Membrane fluidity, Methamphetamine, Sex differences,
• MeSH
• corpus striatum účinky léků   metabolismus   MeSH
• dopamin metabolismus   MeSH
• krysa rodu Rattus MeSH
• methamfetamin aplikace a dávkování   toxicita   MeSH
• novorozená zvířata MeSH
• pohlavní dimorfismus * MeSH
• potkani Wistar MeSH
• proteiny přenášející dopamin přes plazmatickou membránu metabolismus   MeSH
• těhotenství MeSH
• zpožděný efekt prenatální expozice chemicky indukované   metabolismus   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
• dopamin MeSH
• methamfetamin MeSH
• proteiny přenášející dopamin přes plazmatickou membránu MeSH