Most cited article - PubMed ID 31928040
Review of long-term consequences of maternal methamphetamine exposure
BACKGROUND: Methamphetamine (MA) is a highly abused psychostimulant across all age groups including pregnant women. Because developing brain is vulnerable by the action of drugs, or other noxious stimuli, the aim of our study was to examine the effect of early postnatal administration of MA alone or in combination with enriched environment (EE) and/or stress of separate housing, on the levels of serotonin (5HT) in the hippocampus of male rat pups at three stages of adolescence (postnatal day (PND) 28, 35 and 45). MA (5 mg/kg/ml) was administered subcutaneously (sc) to pups (direct administration), or via mothers' milk between PND1 and PND12 (indirect administration). Controls were exposed saline (SA). Pups were exposed to EE and/or to separation from the weaning till the end of the experiment. RESULTS: On PND 28, in sc-treated series, EE significantly increased the muted 5HT in SA pups after separation and restored the pronounced inhibition of 5HT by MA. No beneficial effect of EE was present in pups exposed to combination of MA and separation. 5HT development declined over time; EE, MA and separation had different effects on 5HT relative to adolescence stage. CONCLUSIONS: Present study shows that MA along with environment or housing affect 5HT levels, depending on both the age and the method of application (direct or indirect). These findings extend the knowledge on the effects of MA alone and in combination with different housing conditions on the developing brain and highlight the increased sensitivity to MA during the first few months after birth.
- Keywords
- Adolescence, Enriched environment, Hippocampus, Methamphetamine, Serotonin,
- Publication type
- Journal Article MeSH
Neurotrophins are proteins included in development and functioning of various processed in mammalian organisms. They are important in early development but as well as during adulthood. Brain - derived neurotrophic factor (BDNF) and nerve growth factor (NGF) have been previously linked with many psychiatric disorders such as depression and addiction. Since during postnatal development, brain undergoes various functional and anatomical changes, we included preweaning environment enrichment (EE), since enrichment has been linked with improved function and development of the several brain structure such as hippocampus (HP), in which we monitored these changes. On the other hand, social isolation has been linked with depression and anxiety-like behavior, therefore postweaning social isolation has been added to this model as well and animal were exposed to this condition till adolescence. We examined if all these three factors had impact on BDNF and NGF levels during three phases of adolescence - postnatal days (PDs) 28, 35 and 45. Our results show that EE did not increase BDNF levels neither in control or MA exposed animals and these results are similar for both direct and indirect exposure. On the other side, social separation after weaning did reduce BDNF levels in comparison to standard housing animals but this effect was reversed by direct MA exposure. In terms of NGF, EE environment increased its levels only in indirectly exposed controls and MA animals during late adolescence. On the other hand, social separation increased NGF levels in majority of animals.
- MeSH
- Hippocampus MeSH
- Rats MeSH
- Methamphetamine * pharmacology MeSH
- Brain metabolism MeSH
- Brain-Derived Neurotrophic Factor * metabolism MeSH
- Nerve Growth Factor metabolism MeSH
- Prenatal Exposure Delayed Effects * MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Methamphetamine * MeSH
- Brain-Derived Neurotrophic Factor * MeSH
- Nerve Growth Factor MeSH
Drug addiction and its effect on the behavior and development of children has become a serious problem in our society. Methamphetamine (MA) is one of the most abused psychostimulants in the Czech Republic, and its abuse is rising worldwide. Previous studies have demonstrated the adverse long-term effects of maternal drug abuse on rat offspring. However, the father's contribution as a parent and donor of half of the genetic information is unclear. Previous studies of other psychostimulant drugs indicate that long-term application of MA to adult male rats may induce changes in their reproductive system and lead to changes in rat pup functional and behavioral development. Therefore, the present review aimed to investigate the effect of MA administration on reproductive toxicity and sexual behavior of adult male rats, as well as the impact of paternal MA exposure on behavioral development and locomotor activity in rat offspring.
- MeSH
- Behavior, Animal MeSH
- Child MeSH
- Adult MeSH
- Rats MeSH
- Humans MeSH
- Methamphetamine * adverse effects MeSH
- Genitalia MeSH
- Rats, Wistar MeSH
- Sexual Behavior MeSH
- Central Nervous System Stimulants * pharmacology MeSH
- Prenatal Exposure Delayed Effects * chemically induced MeSH
- Animals MeSH
- Check Tag
- Child MeSH
- Adult MeSH
- Rats MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
- Names of Substances
- Methamphetamine * MeSH
- Central Nervous System Stimulants * MeSH
Methamphetamine (MA), as massively abused psychoactive stimulant, has been associated with many neurological diseases. It has various potent and neurotoxic properties. There are many mechanisms of action that contribute to its neurotoxic and degenerative effects, including excessive neurotransmitter (NEU) release, blockage of NEU uptake transporters, degeneration of NEU receptors, process of oxidative stress etc. MA intoxication is caused by blood-brain barrier disruption resulted from MA-induced oxidation stress. In our laboratory we constantly work on animal research of MA. Our current interest is to investigate processes of MA-induced alteration in neurotransmission, especially during development of laboratory rat. This review will describe current understanding in role of NEUs, which are affected by MA-induced neurotoxicity caused by altering the action of NEUs in the central nervous system (CNS). It also briefly brings information about NEUs development in critical periods of development.
- MeSH
- Central Nervous System drug effects growth & development metabolism MeSH
- Behavior, Animal drug effects MeSH
- Rats MeSH
- Humans MeSH
- Methamphetamine toxicity MeSH
- Synaptic Transmission drug effects MeSH
- Neurogenesis drug effects MeSH
- Neurotoxicity Syndromes etiology metabolism pathology MeSH
- Neurotransmitter Agents toxicity MeSH
- Central Nervous System Stimulants toxicity MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
- Names of Substances
- Methamphetamine MeSH
- Neurotransmitter Agents MeSH
- Central Nervous System Stimulants MeSH
Methylphenidate is commonly used for the treatment of attention deficit hyperactivity disorder. The cardiovascular safety of methylphenidate has been a subject of debate with some studies indicating that methylphenidate increases the likelihood of experiencing a myocardial infarction. However, it is unknown whether methylphenidate worsens the extent of injury during an ischemic insult. The purpose of this study was to determine whether short term exposure to methylphenidate increases the extent of myocardial injury during an ischemic insult. Male and female rats received methylphenidate (5 mg/kg/day) or saline for 10 days by oral gavage. Hearts were subjected to 20 min of ischemia and 2 h of reperfusion on a Langendorff isolated heart apparatus on day 11. Cardiac contractile function was monitored via an intraventricular balloon and myocardial injury was assessed by triphenyltetrazolium chloride staining. Methylphenidate significantly increased locomotor activity in male and female rats, confirming absorption of this psychostimulant into the central nervous system. Male hearts had significantly larger infarcts than female hearts, but methylphenidate had no impact on infarct size or postischemic recovery of contractile function in hearts of either sex. These data indicate that methylphenidate does not increase the extent of injury induced by an ischemic insult.
- MeSH
- Myocardial Infarction chemically induced pathology MeSH
- Myocardial Ischemia chemically induced pathology MeSH
- Myocardial Contraction drug effects MeSH
- Rats MeSH
- Methylphenidate adverse effects pharmacology MeSH
- Disease Models, Animal MeSH
- Recovery of Function MeSH
- Rats, Sprague-Dawley MeSH
- Drug Administration Schedule MeSH
- Central Nervous System Stimulants pharmacology MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Methylphenidate MeSH
- Central Nervous System Stimulants MeSH
Methamphetamine (MA), a psychostimulant, has become a serious problem in recent years. It is one of the most widely abused psychostimulants in the world. In the Czech Republic, ecstasy is the most commonly used non-cannabis drug, followed by hallucinogenic fungi, LSD, MA, cocaine, and finally heroin. The prevalence of the usage of all addictive substances is highest in the age category of 15-34. Approximately 17.2% of registered drug addicts, both male and female, in the Czech Republic use MA as their first-choice drug. This group consists mostly of women who are unemployed and addicted to MA (85%). Almost half of the addicted women switched to MA from other drugs in the course of pregnancy. Psychostimulants such as amphetamine and its synthetic derivate MA induce feelings of calm and happiness by suppressing anxiety and depression. When MA is abused for longer periods, it mimics symptoms of mania and can lead to the development of psychosis. MA is often abused for its anorectic effect, its simple preparation, and compared to heroin and cocaine, its low price. There are significant differences in the susceptibility of users to the stimulant, with reactions to MA fluctuating from person to person. Molecular mechanisms related to the variable response among users might represent an explanation for increased addiction-associated bipolar disorder and psychosis. Currently, there is limited information regarding genetic mechanisms linked to these disorders and the transmission of drug addiction. As such, animal models of drug addiction represent significant sources of information and assets in the research of these issues. The aim of this review is to summarize the mechanism of action of methamphetamine and its effect on pregnant addicted women and their children, including a detailed description of the anatomical structures involved.
- Keywords
- dopamine, drug addiction, hippocampus, methamphetamine, prefrontal cortex, prenatal, serotonin, striatum,
- Publication type
- Journal Article MeSH
- Review MeSH