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.

• Keywords
• hippocampus, methamphetamine, microarray, prefrontal cortex, prenatal, real-time PCR, receptor, striatum,
• Publication type
• Journal Article MeSH

There is accumulating evidence that methamphetamine (MA) is a widely abused drug popular among pregnant women. MA exposure is associated with changes in the function of neurotransmitter systems, namely the dopaminergic, serotonergic and glutamatergic systems. Since N-methyl-D-aspartate receptors (NMDA) are affected by MA-induced glutamate release, we assessed the expression of NMDAR subunits (NR1, NR2A, and NR2B) and postsynaptic density protein 95 (PSD-95), which is connected with NMDAR. We measured the expression of these proteins in adolescent (30 days old) and adult (60 days old) rat males exposed to MA during the entire prenatal period and compared them with the same parameters in age matched saline-exposed rats. There was a significant increase in the NR1 and NR2B subunits in the hippocampus of adult males, but not in adolescent males. We identified a significant change in adult MA-induced rats when compared to adult controls for NR2A and NR2B, while in adolescent MA rats this change was close to the boundary of significance. In summary, our study suggests that prenatal MA exposure is connected with changes in NMDAR subunit expression in adult rats but not in adolescent rats.

• MeSH
• Hippocampus drug effects   metabolism   MeSH
• Methamphetamine toxicity   MeSH
• Animals, Newborn MeSH
• Protein Subunits metabolism   MeSH
• Rats, Sprague-Dawley MeSH
• Receptors, N-Methyl-D-Aspartate metabolism   MeSH
• Signal Transduction drug effects   MeSH
• Aging MeSH
• Pregnancy MeSH
• Prenatal Exposure Delayed Effects metabolism   MeSH
• Animals MeSH
• Check Tag
• Male MeSH
• Pregnancy MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Methamphetamine MeSH
• Protein Subunits MeSH
• Receptors, N-Methyl-D-Aspartate MeSH

Stimulant drugs are often associated with increased seizure susceptibility. Inhibitory gamma-aminobutyric acid (GABA) and excitatory N-methyl-D-aspartate (NMDA) systems play an important role in the effect of stimulants on epileptic seizures. No studies investigating the effect of prenatal methamphetamine (MA) exposure on seizures are available. In this study, bicuculline (GABAA receptor antagonist), NMDA (NMDA receptor agonist) and kainic acid (non-NMDA receptor agonist) were used to induce seizures in adult male rats. Three groups of animals were tested in each seizure test: prenatally MA- (5 mg/kg) exposed, prenatally saline-exposed, and absolute controls without any prenatal exposure. In bicuculline-induced seizures, the latency to onset of tonic-clonic seizures was shorter in MA-exposed rats than in controls, but it did not differ from saline-exposed rats. There were no differences in clonic seizure onset between groups. In NMDA-induced seizures, the latency to onset of clonic-tonic seizures was shorter in prenatally MA-exposed rats than in controls; however, the latency to onset of saline-exposed animals did not differ from either MA-exposed or from control rats. There were no differences in seizure susceptibility in kainic acid-induced clonic seizures. There were no differences in seizure incidences or stereotypical behavior in any seizure model. The question remains as to how much the present data demonstrate the effect of prenatal drug exposure on seizure susceptibility per se, and how much they may be explained by the effect of prenatal stress or by other mechanism(s).

• MeSH
• Excitatory Amino Acid Agonists toxicity   MeSH
• Bicuculline antagonists & inhibitors   toxicity   MeSH
• GABA Antagonists toxicity   MeSH
• Rats MeSH
• Kainic Acid antagonists & inhibitors   toxicity   MeSH
• Methamphetamine therapeutic use   MeSH
• N-Methylaspartate antagonists & inhibitors   toxicity   MeSH
• Rats, Wistar MeSH
• Central Nervous System Stimulants therapeutic use   MeSH
• Pregnancy MeSH
• Seizures chemically induced   prevention & control   MeSH
• Prenatal Exposure Delayed Effects MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Pregnancy MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Excitatory Amino Acid Agonists MeSH
• Bicuculline MeSH
• GABA Antagonists MeSH
• Kainic Acid MeSH
• Methamphetamine MeSH
• N-Methylaspartate MeSH
• Central Nervous System Stimulants MeSH