Methamphetamine (METH) is a widespread illicit drug. If it is taken by pregnant women, it passes through the placenta and just as it affects the mother, it can impair the development of the offspring. The aim of our study was to identify candidates to investigate for changes in the gene expression in the specific regions of the brain associated with addiction to METH in rats. We examined the various areas of the central nervous system (striatum, hippocampus, prefrontal cortex) for signs of impairment in postnatal day 80 in experimental rats, whose mothers had been administered METH (5 mg/kg/day) during the entire gestation period. Changes in the gene expression at the mRNA level were determined by two techniques, microarray and real-time PCR. Results of two microarray trials were evaluated by LIMMA analysis. The first microarray trial detected either up-regulated or down-regulated expression of 2189 genes in the striatum; the second microarray trial detected either up-regulated or down-regulated expression of 1344 genes in the hippocampus of prenatally METH-exposed rats. We examined the expression of 10 genes using the real-time PCR technique. Differences in the gene expression were counted by the Mann-Whitney U-test. Significant changes were observed in the cocaine- and amphetamine-regulated transcript prepropeptide, tachykinin receptor 3, dopamine receptor D3 gene expression in the striatum regions, in the glucocorticoid nuclear receptor Nr3c1 gene expression in the prefrontal cortex and in the carboxylesterase 2 gene expression in the hippocampus of prenatally METH-exposed rats. The microarray technique also detected up-regulated expression of trace amine-associated receptor 7 h gene in the hippocampus of prenatally METH-exposed rats. We have identified susceptible genes; candidates for the study of an impairment related to methamphetamine addiction in the specific regions of the brain.

• Klíčová slova
• hippocampus, methamphetamine, microarray, prefrontal cortex, prenatal, real-time PCR, receptor, striatum,
• Publikační typ
• časopisecké články MeSH

The aim of our study was to reveal whether acute methamphetamine (MA) administration changes the sensitivity to seizures induced by N-methyl-D-aspartate (NMDA) in prenatally MA-exposed adult rats. Adult rats with respect to sex and female estrous cycle (prenatally MA-exposed, prenatally saline-exposed, and controls) were divided into groups with acute MA (1 mg/kg) or without acute drug administration (saline injection). Intraperitoneal administration of 250 mg/kg of NMDA was used as a seizure model. The present study demonstrated that both prenatal MA and prenatal saline exposure decreased the latency to onset of stereotypy and clonic-tonic seizures. Acute MA administration decreased latency to onset of stereotypic behavior in all groups, while increased latency to onset of clonic-tonic seizures in prenatally saline-exposed rats. The duration of NMDA seizures was longer after acute MA administration relative to animals without acute MA pretreatment in both control groups. In addition, males displayed decreased susceptibility to NMDA-induced seizures relative to females regardless of their estrous cycle. Our study suggests that acute MA exposure changes susceptibility to NMDA-induced seizures in respect of prenatal exposure and sex. However, it seems that the effect of prenatal exposure is not induced by the drug per se but rather by the repeated injection exposure that causes prenatal stress.

• MeSH
• agonisté excitačních aminokyselin aplikace a dávkování   toxicita   MeSH
• časové faktory MeSH
• estrální cyklus fyziologie   MeSH
• krysa rodu Rattus MeSH
• methamfetamin farmakologie   MeSH
• N-methylaspartát aplikace a dávkování   toxicita   MeSH
• potkani Wistar MeSH
• rozvrh dávkování léků MeSH
• sexuální faktory MeSH
• stereotypní chování účinky léků   MeSH
• stimulanty centrálního nervového systému farmakologie   MeSH
• těhotenství MeSH
• záchvaty chemicky indukované   MeSH
• zpožděný efekt prenatální expozice 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
• Názvy látek
• agonisté excitačních aminokyselin MeSH
• methamfetamin MeSH
• N-methylaspartát MeSH
• stimulanty centrálního nervového systému MeSH