Methamphetamine (MA) is an addictive psychostimulant with significant potential for abuse. Previous rat studies have demonstrated that MA use during pregnancy impairs maternal behavior and induced delayed development of affected pups. The offspring of drug-addictive mothers were often neglected and exposed to neonatal stressors. The present study therefore examines the effect of perinatal stressors combined with exposure to prenatal MA on the development of pups and maternal behavior. Dams 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 four groups according to postnatal stressors: controls (N); maternal separation (S); maternal cold-water stress (W); maternal separation plus cold-water stress (SW). The pup-retrieval test showed differences among postnatally stressed mothers and non-stressed controls. The righting reflex on a surface revealed delayed development of pups prenatally exposed to MA/SA and postnatal stress. Negative geotaxis and Rotarod results confirmed that the MA group was the most affected. Overall, our data suggests that a combination of perinatal stress and prenatal MA can have a detrimental effect on maternal behavior as well as on the sensorimotor development of pups. However, MA exposure during pregnancy seems to be the decisive factor for impairment.

• MeSH
• krysa rodu rattus MeSH
• maternální deprivace MeSH
• mateřské chování účinky léků   fyziologie   psychologie   MeSH
• methamfetamin toxicita   MeSH
• metoda rotující tyčky metody   psychologie   MeSH
• náhodné rozdělení MeSH
• novorozená zvířata MeSH
• poruchy spojené s užíváním psychoaktivních látek komplikace   patofyziologie   psychologie   MeSH
• potkani Wistar MeSH
• psychický stres komplikace   patofyziologie   psychologie   MeSH
• psychomotorický výkon účinky léků   fyziologie   MeSH
• stimulanty centrálního nervového systému toxicita   MeSH
• těhotenství MeSH
• zpožděný efekt prenatální expozice chemicky indukované   patofyziologie   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

Social behavior involves complex of different forms of interactions between individuals that is essential for healthy mental and physical development throughout lifespan. Psychostimulants, including methamphetamine (MA), have neurotoxic effect, especially, if they are targeting CNS during its critical periods of development. The present study was aimed on evaluation of changes in social interactions (SI) following scheduled prenatal/neonatal MA treatment in combination with acute application in adulthood. Eight groups of male and eight groups of female rats were tested in adulthood: rats, whose mothers were exposed to MA (5mg/ml/kg) or saline (SA, 1ml/kg) during the first half of gestation (ED 1-11), the second half of gestation (ED 12-22) and neonatal period (PD 1-11). To do this, we compared indirect neonatal applications via the exposed dams with group of rat pups that received MA or SA directly through injections. In adulthood, half animals from each group were injected with MA (1mg/kg), second half with saline 45min prior to the Social Interaction Test. Females and males were observed for social and nonsocial activities of two unfamiliar individuals of the same sex and treatment in a familiar Open field arena. The present study demonstrated that prenatal/neonatal MA exposure leads to decrease the time spent in genital investigation, following and nonsocial activity. Acute dose of MA leads to a decrease in all SI patterns and to an increase in nonsocial activities relative to acute SA. Females were more active than males. Animals exposed to prenatal/neonatal treatment during the second half of gestation (ED 12-22) and throughout lactation period (PD 1-11 indirect/direct) had fewer SI and greater exploratory behavior than animals exposed during the first half of gestation (ED 1-11).

• MeSH
• estrální cyklus účinky léků   MeSH
• methamfetamin toxicita   MeSH
• modely nemocí na zvířatech MeSH
• náhodné rozdělení MeSH
• novorozená zvířata MeSH
• pohlavní dimorfismus * MeSH
• pohybová aktivita účinky léků   MeSH
• potkani Wistar MeSH
• sociální chování * MeSH
• stimulanty centrálního nervového systému toxicita   MeSH
• těhotenství MeSH
• zpožděný efekt prenatální expozice psychologie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

• Publikační typ
• abstrakt z konference MeSH

In the present study we investigated the sex differences in the effect of adult long-term drug treatment on cognitive functions of Wistar rats, which were prenatally exposed to MA (5mg/kg) or saline. Cognitive functions were tested as an ability of spatial learning in the Morris Water Maze (MWM), which consisted of three types of tests: "Place Navigation Test"; "Probe Test", and "Memory Recall Test". Adult animals were injected daily, after completion of the last trial, either with saline or cocaine (COC; 5mg/kg), MDMA (3,4-methylenedioxy-methamphetamine; 5mg/kg), morphine (MOR; 5mg/kg), or delta-9-tetrahydrocannabinol (THC; 2mg/kg). Results revealed worsened MWM performance in female rats after drug treatment in adulthood. Not only were traditionally investigated parameters affected by drug treatment (latency of platform acquisition, search strategy, distance traveled), but also strategies used by animals (thigmotaxis, scanning). Analyses of search strategies observed in the Place Navigation Test, as well as in the Memory Recall Test, demonstrated variations in the percentage of time spent in thigmotaxis and scanning in females after treatment with COC, MDMA, MOR, and THC. Although we did not see a sensitizing effect of prenatal MA, in some cases the effect of drug treatment in adulthood differed depending on the prenatal drug exposure. The data presented in this study demonstrates that exposure to drugs with various mechanisms of action alters spatial abilities of female rats in the MWM. Alterations in the effect of adult drug treatment with reference to prenatal drug exposure were also found in the present study.

• MeSH
• kognice účinky léků   MeSH
• kokain farmakologie   MeSH
• methamfetamin toxicita   MeSH
• morfin farmakologie   MeSH
• N-methyl-3,4-methylendioxyamfetamin farmakologie   MeSH
• náhodné rozdělení MeSH
• pohlavní dimorfismus * MeSH
• potkani Wistar MeSH
• prostorová navigace účinky léků   MeSH
• prostorové učení účinky léků   MeSH
• psychologické testy MeSH
• psychotropní léky farmakologie   MeSH
• těhotenství MeSH
• tetrahydrokanabinol farmakologie   MeSH
• zpožděný efekt prenatální expozice psychologie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Since it enters breast milk, methamphetamine (MA) abuse during lactation can not only affect the quality of maternal behavior but also postnatal development of pups. The aim of the present study was to examine the effect of injected MA (5mg/kg) on maternal behavior of rats and the differences in postnatal development, during postnatal days (PD) 1-11, of pups when the pups were directly exposed (i.e., injected) to MA or received MA indirectly via breast milk. Maternal behavior was examined using observation test (PD 1-22) and pup retrieval test (PD 1-12). The following developmental tests were also used: surface righting reflex (PD 1-12), negative geotaxis (PD 9), mid-air righting reflex (PD 17), and the rotarod and beam-balance test (PD 23). The weight of the pups was recorded during the entire testing period and the day of eye opening was also recorded. MA-treated mothers groomed their pups less and returned the pups to the nest slower than control dams. The weight gain of pups indirectly exposed to MA was significantly slower. In addition, pups indirectly exposed to MA were slower on the surface righting reflex (on PD 1 and PD 2) and the negative geotaxis test. In females, indirect exposure to MA led to earlier eye opening compared to controls. At the end of lactation, males who received MA indirectly via breast milk performed worse on the balance beam test compared to males who received MA directly. However, direct exposure to MA improved performance on rotarod relative to controls. Our results suggest that indirect MA exposure, via breast milk, has a greater impact than direct MA exposure.

• MeSH
• analýza rozptylu MeSH
• embryo savčí MeSH
• krysa rodu rattus MeSH
• lokomoce účinky léků   MeSH
• mateřské chování účinky léků   MeSH
• methamfetamin toxicita   MeSH
• novorozená zvířata MeSH
• polohový reflex účinky léků   MeSH
• potkani Wistar MeSH
• psychomotorický výkon účinky léků   MeSH
• sexuální faktory MeSH
• stimulanty centrálního nervového systému toxicita   MeSH
• těhotenství MeSH
• tělesná hmotnost účinky léků   MeSH
• věkové faktory MeSH
• vztahy mezi matkou a dítětem MeSH
• zpožděný efekt prenatální expozice chemicky indukované   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Different forms of anxiety-related behavior have been reported after a single drug use of many abused substances, however, less is known about how males and females are affected differently from exposure to various drugs. Furthermore, chronic prenatal methamphetamine (MA) exposure was shown to predispose the animal to an increased sensitivity to drugs administrated in adulthood. Using the Elevated plus-maze test (EPM), the first aim of the present study was to examine how male and female rats are affected by acute drug treatment with subcutaneously (s.c.) administrated (a) MA (1mg/kg); (b) drugs with a similar mechanism of action to MA: amphetamine (AMP, 1mg/kg), cocaine (COC, 5mg/kg), 3,4-methylenedioxymethamphetamine (MDMA, 5mg/kg); and (c) drugs with different mechanisms of action: morphine (MOR, 5mg/kg), and Δ 9-tetrahydrocannabinol (THC, 2mg/kg). The second aim was to determine if prenatally MA-exposed (5mg/kg) animals show an increased sensitivity to adult drug treatment. The parameters analyzed were divided into two categories: anxiety-related behavior and anxiety-unrelated/exploratory behavior. Our results showed in female rats a decreased percentage of the time spent in the closed arms (CA) after MA, and an increased percentage of the time spent in the open arms (OA) after MA, AMP, and COC treatment, indicating an anxiolytic-like effect. In females, MDMA and THC treatment increased the percentage of the time spent in the CA. An increased percentage of the time spent in the CA was also seen after MOR treatment in females as well as in males, indicating an anxiogenic-like effect. As far as the interaction between prenatal MA exposure and adult drug treatment is concerned, there was no effect found. In conclusion, it seems that: (a) in some cases female rats are more vulnerable to acute drug treatment, in terms of either anxiogenic- or anxiolytic-like effects; (b) prenatal MA exposure does not sensitize animals to the anxiety-related effects of any of the drugs.

• MeSH
• analgetika farmakologie   MeSH
• analýza rozptylu MeSH
• bludiště - učení účinky léků   MeSH
• časové faktory MeSH
• estrální cyklus účinky léků   MeSH
• krysa rodu rattus MeSH
• methamfetamin toxicita   MeSH
• N-methyl-3,4-methylendioxyamfetamin farmakologie   MeSH
• pátrací chování účinky léků   MeSH
• serotoninové látky farmakologie   MeSH
• sexuální faktory MeSH
• stimulanty centrálního nervového systému toxicita   MeSH
• těhotenství MeSH
• úzkost chemicky indukované   MeSH
• zpožděný efekt prenatální expozice chemicky indukované   patofyziologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Psychostimulants are known to have a huge impact on different forms of social behaviour. The aim of the present study was to compare the effects of three different psychostimulants [amphetamine, cocaine and 3,4 methylenedimethoxyamphetamine (MDMA)] on social interaction (SI) in adult male rats. The SI test was performed in a familiar arena and under low-stress environmental conditions. Experimental animals received amphetamine (0.5, 1.0, 1.5 mg/kg), cocaine (0.5, 1.0, 1.5, 2.5, 5.0, 10.0 mg/kg) or MDMA (2.5, 5.0, 10 mg/kg) and control animals received saline (1 ml/kg) 45 min before the SI test. Time spent in SI (individual patterns of social behaviour) and nonsocial activities (locomotion and rearing) were video recorded and then analysed offline, with the following results: (a) all doses of amphetamine decreased SI. Specifically, all doses of amphetamine decreased mutual sniffing, and the higher doses also decreased allo-grooming and following behaviours. (b) The higher doses of cocaine decreased SI, especially mutual sniffing, allo-grooming and climbing over. Cocaine at the dose of 5.0 mg/kg increased genital investigation compared with lower doses. (c) All doses of MDMA decreased mutual sniffing and climbing over; the two higher doses decreased allo-grooming behaviour, and only the highest dose decreased following. The two higher doses of amphetamine and all the doses of MDMA increased locomotion and rearing; cocaine did not affect locomotion, but increased rearing at higher doses. In conclusion, the results confirm the well-known finding that psychostimulants suppress SI, but also show novel differences in the effects of psychostimulants on specific patterns of SI.

• MeSH
• amfetamin farmakologie   MeSH
• chování zvířat účinky léků   MeSH
• interpersonální vztahy * MeSH
• kokain farmakologie   MeSH
• krysa rodu rattus MeSH
• lokomoce účinky léků   MeSH
• N-methyl-3,4-methylendioxyamfetamin farmakologie   MeSH
• pohybová aktivita účinky léků   MeSH
• potkani Wistar MeSH
• stimulanty centrálního nervového systému farmakologie   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The present study examined the hypothesis that the extension of noxious effect of methamphetamine (MA) on maternal behavior and postnatal development on the pups may differ in dependence with time of application. Female rats were injected with MA (5 mg/kg) or saline during first (embryonic day (ED) 1-11) or second (ED 12-22) half of gestation. Our results demonstrated that MA exposure on ED 12-22 led to decreased birth weight and weight gained during lactation period relative to rats treated on ED 1-11. Both sexes treated prenatally with MA on ED 1-11 opened eyes earlier compared to animals treated on ED 12-22. As a matter of sensorimotor development application of MA on ED 1-11 impaired the righting reflex, while MA exposure on ED 12-22 impaired the performance of beam balance test in male rats. There were no differences in maternal behavior. Therefore, it seems that MA exposure in the first half of the gestation impaired the early sensorimotor development that is under control of the brain stem, while the MA exposure in the second half of gestation affected the beam balance performance that is dependent on the function of the cerebellum.

• MeSH
• mateřské chování účinky léků   MeSH
• methamfetamin aplikace a dávkování   MeSH
• metoda rotující tyčky MeSH
• náhodné rozdělení MeSH
• novorozená zvířata MeSH
• potkani Wistar MeSH
• růst a vývoj účinky léků   MeSH
• stimulanty centrálního nervového systému aplikace a dávkování   MeSH
• těhotenství MeSH
• zpožděný efekt prenatální expozice * MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

It is known that psychostimulants including methamphetamine (MA) have neurotoxic effect, especially, if they are targeting CNS during its critical periods of development. The present study was aimed on evaluation of cognitive changes following scheduled prenatal MA exposure in combination with long-term exposure in adulthood of male rats. Two periods of gestation were targeted: 1(st) half - the embryonic day (ED) 1-11 and 2(nd) half - ED 12-22. Rat mothers received subcutaneously a daily injection of MA (5 mg/kg) or saline (SAL, 1 ml/kg) throughout scheduled periods. Male offspring were tested for cognitive changes in the Morris Water Maze (MWM) in adulthood. Each day of the experiment animals received an injection of MA (1 mg/kg) or SAL (1 ml/kg) during 12 days. Our results demonstrated that in the group of animals exposed to the drug during ED 1-11, neither prenatal MA exposure, nor adult MA treatment changed the performance in the MWM test. Only the velocity was increased in group with long-term MA treatment (SAL/MA and MA/MA). In the group of animals exposed to the drug during ED 12-22, rats exposed to MA prenatally and also in adulthood (MA/MA) swam faster but learned the position of the platform slower in the Place Navigation Test than animals exposed to SAL in adulthood (MA/SAL). In the Probe Test, MA/SAL had decreased velocity and swam shorter distance than MA/MA or SAL/SAL rats suggesting increased floating of these animals. In the Memory Retention Test, SAL/MA rats swam shorter distance than SAL/SAL or MA/MA animals suggesting changes in used strategies in memory recall. As conclusion, our results suggest differences in the effect of combination of prenatal and adult exposure to MA. These effects further depend on the stage of CNS development and schedule of MA exposure affecting intrauterine development in male rats.

• MeSH
• bludiště - učení účinky léků   MeSH
• kognice účinky léků   MeSH
• methamfetamin aplikace a dávkování   toxicita   MeSH
• náhodné rozdělení MeSH
• potkani Wistar MeSH
• retence (psychologie) účinky léků   MeSH
• stimulanty centrálního nervového systému aplikace a dávkování   toxicita   MeSH
• těhotenství MeSH
• zpožděný efekt prenatální expozice * MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH