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
Behavioral sensitization is defined as augmented psychomotor activity, which can be observed after drug re-administration following withdrawal of repeated drug exposure. It has been shown that abuse of one drug can lead to increased sensitivity to certain other drugs. This effect of developed general drug sensitivity is called cross-sensitization and has been reported between drugs with similar as well as different mechanisms of action. There is growing evidence that exposure to drugs in utero not only causes birth defects and delays in infant development, but also impairs the neural reward pathways, in the brains of developing offspring, in such a way that it can increase the tendency for drug addiction later in life. This review summarizes the results of preclinical studies that focused on testing behavioral cross-sensitization, after prenatal Methamphetamine exposure, to drugs administered in adulthood, with both similar and different mechanisms of action. Traditionally, behavioral sensitization has been examined using the Open field or the Laboras Test to record locomotor activity, and the Conditioned Place Preference and Self-administration test to examine drug-seeking behavior. However, it seems that prenatal drug exposure can sensitize animals not only to the locomotor-stimulating and conditioning effects of drugs, but may also be responsible for modified responses to various drug effects.
- MeSH
- lidé MeSH
- lokomoce účinky léků fyziologie MeSH
- methamfetamin aplikace a dávkování škodlivé účinky MeSH
- modely u zvířat * MeSH
- poruchy spojené s užíváním psychoaktivních látek etiologie metabolismus psychologie MeSH
- stimulanty centrálního nervového systému aplikace a dávkování MeSH
- těhotenství MeSH
- zpožděný efekt prenatální expozice chemicky indukované metabolismus psychologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy 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
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
Už několik let dominuje metamfetamin (MA) drogovému trhu jak v České republice, tak na Slovensku, avšak alarmující je i jeho spotřeba celosvětově. Stále rostoucí počet studií poukazuje na fakt, že vystavení MA in utero nezpůsobuje jenom vývojové vady a poruchy ve vývoji centrálního nervového systému, ale může vést k takovým změnám ve vyvíjejícím se systému odměny mozku, které zvýší pravděpodobnost k rozvoji drogové závislosti později v životě. Dostupné studie na animálních modelech poukazují na fakt, že potomci matek, kteří byli vystaveni prenatálně účinkům MA, jsou citlivější k aplikaci MA v dospělosti. Pro zvýšenou citlivost na účinky drogy byl zaveden termín senzitizace a ta je definována jako zvýšená psychomotorická aktivita po jednorázové aplikaci drogy, když dříve došlo k návyku na tuto drogu. Senzitizace byla pozorována nejen po opakovaném podávání drogy v dospělosti, ale také po chronické prenatální expozici účinkům drogy. Výsledky našich studií ukazují, že prenatální expozice MA zvyšuje citlivost k účinku aplikace drog v dospělosti, konkrétně k těm s podobným mechanismem účinku.
Women, who abuse drugs during pregnancy, expose not just themselves but also their developing fetus to impairing effects, which can have potentially harmful and even long-term effects on the exposed children. For some years, methamphetamine (MA) has dominated the illicit drug market in the Czech Republic and Slovakia; additionally this drug is on the rise worldwide. It is one of the most accessible drugs, and in many cases the first choice drug for many drug-addicted pregnant women; in part due to its anorectic and stimulant effects. These women are rarely aware of the consequences of their behavior and their pregnancy is hardly ever a good enough reason for giving up drug use. These findings are supported by many experimental studies that show the damaging effects of maternal MA exposure on their offspring. There is growing evidence that exposure to MA in utero not only causes birth defects and delays in infant development, but also impairs the brain reward neural pathways of a developing offspring in such a way, that it could increase the predisposition for drug addiction later in life. Previously published animal studies have shown that offspring of mothers exposed to MA during pregnancy are more sensitive to MA when they encounter this drug later in adulthood. With respect to increased sensitivity, the term of sensitization has been introduced. It is defined as augmented psychomotor activity, which can be observed after drug re-administration following discontinuation of repeated drug exposure, and has been demonstrated to develop not only after repeated drug administration in adulthood, but also after chronic prenatal exposure. Results from our studies have shown that prenatal MA exposure can influence the sensitivity to the effects of some drugs, given as a challenge, in adulthood, specifically to those with a similar action mechanism. Our findings indicate that cross-sensitization between prenatal MA exposure and adult drug treatment cannot be simply termed as a general drug addiction, since it seems that the mechanism by which a drug impairs specific neurotransmitter systems plays an important role. The study findings show that although the offspring of MA-addicted mothers have altered sensitivity to certain drugs in adulthood, they do not display increased active drug-seeking behavior. Therefore, if we extrapolate the results to humans, it appears that there is a relatively little risk that a person, whose mother abused MA during pregnancy, will actively seek out drugs.
- MeSH
- chování zvířat účinky léků MeSH
- dopamin metabolismus MeSH
- kanabinoidy farmakologie MeSH
- krysa rodu rattus MeSH
- lidé MeSH
- matka - expozice noxám MeSH
- methamfetamin farmakologie MeSH
- modely nemocí na zvířatech MeSH
- návykové chování * chemicky indukované patofyziologie MeSH
- nucleus accumbens metabolismus MeSH
- opioidní analgetika farmakologie MeSH
- poruchy spojené s užíváním amfetaminu patofyziologie MeSH
- poruchy spojené s užíváním psychoaktivních látek * patofyziologie MeSH
- stimulanty centrálního nervového systému farmakologie MeSH
- tegmentum mesencephali - area ventralis metabolismus MeSH
- těhotenství účinky léků MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zpožděný efekt prenatální expozice * MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- lidé MeSH
- těhotenství účinky léků MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
The aim of the present study was to compare effect of three low doses of morphine (MOR) and delta9-tetrahydrocannabinol (THC) on social behavior tested in Social interaction test (SIT). 45 min prior to testing adult male rats received one of the drugs or solvents: MOR (1; 2.5; 5 mg/kg); saline as a solvent for MOR; THC (0.5; 1; 2 mg/kg); ethanol as a solvent for THC. Occurrence and time spent in specific patterns of social interactions (SI) and non-social activities (locomotion and rearing) was video-recorded for 5 min and then analyzed. MOR in doses of 1 and 2.5 mg/kg displayed decreased SI in total. Detailed analysis of specific patterns of SI revealed decrease in mutual sniffing and allo-grooming after all doses of MOR. The highest dose (5 mg/kg) of MOR decreased following and increased genital investigation. Rearing activity was increased by lower doses of MOR (1 and 2.5 mg/kg). THC, in each of the tested doses, did not induce any specific changes when compared to matching control group (ethanol). However, an additional statistical analysis showed differences between all THC groups and their ethanol control group when compared to saline controls. There was lower SI in total, lower mutual sniffing and allo-grooming, but higher rearing in THC and ethanol groups than in saline control group. Thus, changes seen in THC and ethanol groups are seemed to be attributed mainly to the effect of the ethanol. Based on the present results we can assume that opioids affect SI more than cannabinoid.
