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
- Publikační typ
- abstrakt z konference 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