Methamphetamine (MA) is a drug causing potent psychomotor activation. The aim of the present study was: (1) to assess the effect of prenatal and acute MA administration on behavior in adult male rats and (2) to find out if the prenatal exposure to MA increases sensitivity to acute MA application in adulthood. Behavior of adult male rats prenatally exposed to MA (5mg/kg) or saline was tested in Open field (OF) and Elevated plus maze (EPM). Subcutaneously administered MA (1mg/kg) or saline were used as challenge in adulthood, 30 min prior to testing. Our results showed that prenatal MA did not have an effect on baseline behavior in either of the tests. By contrast, acute MA increased overall psychomotor activity by increasing locomotion and exploratory behavior and decreasing comforting behavior. Moreover, adult rats prenatally exposed to MA exhibited increased sniffing and decreased rearing after acute MA dose in adulthood relative to prenatally saline-exposed rats. In addition, while acute MA application decreased anxiety in rats prenatally exposed to MA, rats prenatally exposed to saline were less sensitive to the anxiolytic effects of MA. Our results indicate that changes caused by prenatal exposure to psychostimulants may become apparent as different reactivity to drugs of abuse when an individual encounters them later in life. In addition, we found that the anxiolytic effect of acute MA (1mg/kg) probably depends also on the reactivity to stress and the activity of hypothalamo-pituitary-adrenal axis.

• MeSH
• bludiště - učení účinky léků   MeSH
• krysa rodu rattus MeSH
• methamfetamin aplikace a dávkování   farmakologie   MeSH
• pátrací chování účinky léků   MeSH
• pohybová aktivita účinky léků   MeSH
• potkani Wistar MeSH
• stimulanty centrálního nervového systému aplikace a dávkování   farmakologie   MeSH
• těhotenství MeSH
• úzkost farmakoterapie   MeSH
• zpožděný efekt prenatální expozice 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
• 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

Prenatal stress and drug exposure induce permanent alterations of the brain. Even though different brain structures are involved, alterations almost always refer to the hippocampus. The aim of this study was to investigate the excitability of hippocampal slices in low-magnesium epilepsy model of prenatally methamphetamine (MA, 5mg/kg sc.) or saline (sc., stress model) exposed animals in adult male rats. The second aim was to investigate, if a low dose of MA (1ml/kgs.c.) administered in adulthood changes the hippocampal activity of these animals. Adult Wistar male rats were divided into groups according to their prenatal treatment (C - naïve control; Sa - saline; MA - MA administration). One half of the animals was treated with a challenge dose of MA (1mg/kg sc.) 45min before hippocampal slices were cut. The activity of 350μ thick transversal slices of CA1 hippocampi was recorded (latencies of the first epileptiform discharge and the regular epileptiform activity) and evaluated in ACSF with low-magnesium concentration. Effects of prenatal exposure: The highest excitability was found in the Sa (prenatally stressed) group in respect to C and MA groups. This group developed also the highest number of seizure-like events. In addition, the prenatally MA treated group had also higher excitability than C group. Effects of the MA challenge dose: The challenge dose decreased the excitability of prenatally SA- exposed group. To conclude, even a mild prenatal stress significantly increases hippocampal excitability in adulthood and a challenge dose of MA is able to dampen it.

• MeSH
• epilepsie etiologie   patofyziologie   MeSH
• hipokampus účinky léků   růst a vývoj   patofyziologie   MeSH
• methamfetamin toxicita   MeSH
• modely nemocí na zvířatech MeSH
• náhodné rozdělení MeSH
• nedostatek hořčíku MeSH
• potkani Wistar MeSH
• psychický stres * patofyziologie   MeSH
• techniky tkáňových kultur MeSH
• těhotenství MeSH
• vztah mezi dávkou a účinkem léčiva 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