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
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
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
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
The aim of this study was to investigate the effect of prenatal methamphetamine (MA) exposure and application of the same drug in adulthood on cognitive functions of adult female rats. Animals were prenatally exposed to MA (5 mg/kg) or saline (control group). The cognitive function was tested as ability of spatial learning in the Morris Water Maze (MWM). Each day of the experiment animals received an injection of MA (1 mg/kg) or saline. Our results demonstrated that prenatal MA exposure did not affect the latency to reach the hidden platform or the distance traveled during the Place Navigation Test; however, the speed of swimming was increased in prenatally MA-exposed rats compared to controls regardless of the treatment in adulthood. MA treatment in adulthood increased the latency and distance when compared to controls regardless of the prenatal exposure. Neither prenatal exposure, nor treatment in adulthood affected memory retrieval. As far as the estrous cycle is concerned, our results showed that prenatally MA-exposed females in proestrus/estrus swam faster than females in diestrus. This effect of estrous cycle was not apparent in control females. In conclusion, our results indicate that postnatal, but not prenatal exposure to MA affects learning of adult female rats.
- MeSH
- bludiště - učení účinky léků MeSH
- kognice účinky léků MeSH
- kognitivní poruchy chemicky indukované patofyziologie MeSH
- krysa rodu rattus MeSH
- methamfetamin toxicita MeSH
- novorozená zvířata MeSH
- potkani Wistar MeSH
- sexuální faktory MeSH
- stimulanty centrálního nervového systému otrava MeSH
- těhotenství MeSH
- zpožděný efekt prenatální expozice chemicky indukované patofyziologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
