Effects Of Prenatal Methamphetamine Exposure Research Articles

Maternal inulin supplementation ameliorates prenatal methamphetamine exposure-induced hepatotoxicity and restores gut microbiota in mouse offspring

Prenatal exposure to methamphetamine (METH) is an issue of global concern due to its adverse effects on offspring, particularly its impact on liver health, an area still not fully understood. Inulin, a recognized prebiotic, is thought to potentially ameliorate these developmental disorders and toxic injuries in progeny. To investigate the effects of prenatal METH exposure on the liver and the role of gut microbiota, we established a murine model, the subjects of which were exposed to METH prenatally and subsequently treated with inulin. Our findings indicate that prenatal METH exposure causes liver damage in offspring, as evidenced by a decreased liver index, histopathological changes, diminished glycogen synthesis, hepatic dysfunction, and alterations in mRNA profiles. Furthermore, it impairs the antioxidant system and induces oxidative stress, possibly due to changes in cecal microbiota and dysregulation of bile acid homeostasis. However, maternal inulin supplementation appears to restore the gut microbiota in offspring and mitigate the hepatotoxic effects induced by prenatal METH exposure. Our study provides definitive evidence of METH's transgenerational hepatotoxicity and suggests that maternal inulin supplementation could be an effective preventive strategy.

Maternal use of methamphetamine induces sex-dependent changes in myocardial gene expression in adult offspring.

Methamphetamine is a commonly abused illicit stimulant that has prevalent use among women of child-bearing age. While there are extensive studies on the neurological effects of prenatal methamphetamine exposure, relatively little is known about the effect of prenatal methamphetamine on the adult cardiovascular system. Earlier work demonstrated that prenatal methamphetamine exposure sex dependently (females only) sensitizes the adult heart to ischemic injury. These data suggest that prenatal exposure to methamphetamine may induce sex-dependent changes in cardiac gene expression that persist in adult offspring. The goal of this study was to test the hypothesis that prenatal methamphetamine exposure induces changes in cardiac gene expression that persist in the adult heart. Hearts of prenatally exposed female offspring exhibited a greater number of changes in gene expression compared to male offspring (184 changes compared with 74 in male offspring and 89 changes common between both sexes). Dimethylarginine dimethylaminohydrolase 2 and 3-hydroxybutyrate dehydrogenase 1 (genes implicated in heart failure) were shown by Western Blot to be under expressed in adult females that were prenatally exposed to methamphetamine, while males were deficient in 3-Hydroxybutyrate Dehydrogenase 1 only. These data indicate that prenatal methamphetamine exposure induces changes in gene expression that persist into adulthood. This is consistent with previous findings that prenatal methamphetamine sex dependently sensitizes the adult heart to ischemic injury and may increase the risk of developing cardiac disorders during adulthood.

Prenatal methamphetamine exposure causes dysfunction in glucose metabolism and low birthweight.

Methamphetamine (METH) is a psychostimulant drug that induces addiction. Previous epidemiological studies have demonstrated that maternal METH abuse during pregnancy causes low birthweight (LBW) in the offspring. As a source of essential nutrients, in particular glucose, the placenta plays a key role in fetal development. LBW leads to health problems such as obesity, diabetes, and neurodevelopmental disorders (NDDs). However, the detailed mechanism underlying offspring's LBW and health hazards caused by METH are not fully understood. Therefore, we investigated the effects of prenatal METH exposure on LBW and fetal-placental relationship by focusing on metabolism. We found dysfunction of insulin production in the pancreas of fetuses exposed to METH. We also found a reduction of the glycogen cells (GCs) storing glycogens in the junctional zone of placenta, all of which suggest abnormal glucose metabolism affects the fetal development. These results suggest that dysfunction in fetal glucose metabolism may cause LBW and future health hazards. Our findings provide novel insights into the cause of LBW via the fetal-placental crosstalk.

Effects of prenatal methamphetamine exposure on spatial cognition and hippocampal synaptic plasticity in adolescent rats.

Global rise in methamphetamine (MA) abuse during pregnancy has placed a large number of children at risk for the adverse consequences of prenatal methamphetamine exposure (PME). While behavioral and neurocognitive deficits of PME have been extensively studied in humans and adult rodents, far less is known regarding the sex- and dose-dependent effects of PME as well as the underlying mechanisms. Adolescence in nonhuman primates is also a less explored territory. In the present study, PME was inducted by oral treatment to pregnant rats on gestational days 15-19 with either low dose (0.1mg/ml) or high dose (0.6mg/ml) of MA. The cognitive effects of PME were then evaluated in two adolescence age-intervals: early adolescent (started on postnatal day [PND] 21) and mid-adolescent (started on PND 33), among male and female rat offspring using Morris water maze (MWM) test. Alterations in hippocampal synaptic plasticity in Schaffer collaterals-CA1 pathway were also measured in vitro. Results of behavioral test showed that PME led to serious deficits of learning and memory abilities in both male and female rat offspring. PME also depressed LTP in most of the PME subgroups. Moreover, 21-day-old rats were more sensitive to PME-induced cognitive impairment in MWM tasks, but not in hippocampal synaptic plasticity, than 33-day-old rats. No sex-dependent effects of PME were found on the cognitive function and synaptic plasticity. These findings confirmed that PME impacted negatively on cognitive performance in prepubertal male and female rats, and the impairment of hippocampal synaptic functions might partly play a significant role in these effects.

Neuronal growth and synaptogenesis are inhibited by prenatal methamphetamine exposure leading to memory impairment in adolescent and adult mice

Synaptogenesis plays critical roles in learning and memory processes and is susceptible to substance abuse toxicity. The present study aimed to elucidate the long-lasting effects of prenatal methamphetamine exposure on synaptogenesis and learning and memory. The involvement of BDNF-TrkB signaling was also investigated. Pregnant mice (C57BL/6 JNc) were administered methamphetamine (5 mg/kg, s.c.) on gestation days 8−15. Primary hippocampal cultures were prepared from fetuses at gestational day 16.5 to study neuronal morphology and synaptogenesis. The expression of synaptic proteins, BDNF and TrkB receptor was determined in postnatal day 14 (PND14), adolescent and adult mice; memory tests were also conducted. MA exposure decreased axon length and diameter, and synaptic areas in the primary cultures. Presynaptic protein was decreased in the hippocampus of PND14 mice prenatally exposed to MA, while increases in postsynaptic protein (PSD-95) were found in MA-exposed adolescent and adult mice. BDNF expression was enhanced in the prefrontal cortex and striatum of MA-exposed PND14 mice. Memory impairment was observed in MA-exposed adolescent and adult mice compared to control mice. Prenatal MA exposure disrupted neuronal growth and synapse formation in the developing brain with only short-term interference of the BDNF-TrkB signaling pathway, resulting in the adaptation of postsynaptic neurons. Alterations in the developing brain and synaptogenesis lead to long-lasting learning and memory impairment.

Effects of Prenatal Methamphetamine Exposure on the Developing Human Brain: A Systematic Review of Neuroimaging Studies.

Methamphetamine (MA) can cross the placenta in pregnant women and cause placental abruption and developmental alterations in offspring. Previous studies have found prenatal MA exposure effects on the social and cognitive performance of children. Recent studies reported some alterations in structural and functional magnetic resonance imaging (MRI) of prenatal MA-exposed offspring. In this study, we aimed to investigate the effect of prenatal MA exposure on brain development using recently published structural, metabolic, and functional MRI studies. According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we searched PubMed and SCOPUS databases for articles that used each brain imaging modality in prenatal MA-exposed children. Seventeen studies were included in this study. We investigated brain imaging alterations using 17 articles with four different modalities, including structural MRI, diffusion tensor imaging (DTI), magnetic resonance spectroscopy (MRS), and functional MRI (fMRI). The participants’ age range was from infancy to 15 years. Our findings demonstrated that prenatal MA exposure is associated with macrostructural, microstructural, metabolic, and functional deficits in both cortical and subcortical areas. However, the most affected regions were the striatum, frontal lobe, thalamus and the limbic system, and white matter (WM) fibers connecting these regions. The findings from our study might have valuable implications for targeted treatment of neurocognitive and behavioral deficits in children with prenatal MA exposure. Even so, our results should be interpreted cautiously due to the heterogeneity of the included studies in terms of study populations and methods of analysis.

The Adverse Effects of Prenatal METH Exposure on the Offspring: A Review.

Abuse of methamphetamine (METH), an illicit psychostimulant, is a growing public health issue. METH abuse during pregnancy is on the rise due to its stimulant, anorectic, and hallucinogenic properties. METH can lead to multiple organ toxicity in adults, including neurotoxicity, cardiovascular toxicity, and hepatotoxicity. It can also cross the placental barrier and have long-lasting effects on the fetus. This review summarizes neurotoxicity, cardiovascular toxicity, hepatotoxicity, toxicity in other organs, and biomonitoring of prenatal METH exposure, as well as the possible emergence of sensitization associated with METH. We proposed the importance of gut microbiota in studying prenatal METH exposure. There is rising evidence of the adverse effects of METH exposure during pregnancy, which are of significant concern.

Prenatal Methamphetamine Exposure: Effects on Child Development–A Systematic Review.

In Germany, the 12-month prevalence of methamphetamine use among persons aged 15 to 34 is 1.9%. An increasing number of newborns are being born after a prenatal methamphetamine exposure (PME). In 2014, in the German state of Saxony, approximately four out of 1000 newborns were affected. This systematic review (Prospero registration number CRD42017060536) includes publications that were published between January 1990 and November 2019. The purpose was to determine the effects of PME on the peri- and neonatal condition of the affected children and on their further long-term development. Observational studies with a control group were included in the review and examined for their methodological quality. 31 publications, which dealt with two prospective and six retrospective cohort studies, were included in the review. The studies involved a total of 4446 mother-child pairs with PME, compared with 43 778 pairs without PME. A metaanalysis revealed that PME was associated with, among other findings, lower birth weight (SMD = -0.348; 95% confidence interval [-0.777; 0.081]), shorter body length (SMD= -0.198 [-0.348; -0.047]), and smaller head circumference (SMD= -0.479 [-1.047; 0.089]). Some differences between the groups with and without PME persist into the toddler years. Moreover, children with PME much more commonly display psychological and neurocognitive abnormalities, which are more severe in children growing up in problematic surroundings (discord, violence, poverty, low educational level of the parent or caregiver). A limitation of this review is that not all studies employed an objective or quantitative measure of methamphet - amine use. The documented effects of PME on child development necessitate early treatment of the affected expectant mothers, children, and families. Emphasis should be placed on structured and interdisciplinary preventive measures for methamphetamine use.

Prenatal exposure to methamphetamine in rats induces endothelial dysfunction in male but not female adult offspring.

In utero exposure to methamphetamine results in significant developmental, neurological, and behavioral deficits in offspring. However, very little is known about the cardiovascular effects of prenatal methamphetamine exposure in adult offspring. We hypothesized that prenatal methamphetamine exposure causes adverse cardiovascular effects in adult offspring. The aims of this study were to test the effects of prenatal methamphetamine exposure on blood pressure and endothelial function in male and female adult rat offspring. Pregnant rats were injected with methamphetamine (5mgkg-1day-1) or saline throughout pregnancy. Conscious blood pressure and vascular function in mesenteric-resistance arteries were measured in male and female adult offspring using tail cuff and myography, respectively (beginning at 8weeks old). In adult male offspring, but not in adult female offspring, endothelium-dependent relaxation to acetylcholine was impaired in methamphetamine-exposed compared to saline-exposed rats. Vascular relaxation to diethylamine NONOate diethylammonium salt was not impacted by gender or prenatal exposure. Prenatal methamphetamine exposure had no effect on systolic blood pressure in offspring of either gender. These data suggest that prenatal methamphetamine exposure adversely affects endothelial function in a sex-dependent manner. Clinically, these data suggest that adult males with a history of prenatal methamphetamine exposure may be at greater risk of developing cardiovascular disease due to endothelial dysfunction.

Behavior Problems During Early Childhood in Children With Prenatal Methamphetamine Exposure.

The effects of in utero methamphetamine exposure on behavioral problems in school-aged children are unclear. Our objective for this study was to evaluate behavior problems in children at aged 3, 5, and 7.5 years who were prenatally exposed to methamphetamine. Subjects were enrolled in the Infant Development, Environment, and Lifestyle study, a longitudinal prospective study of prenatal methamphetamine exposure and child outcomes. Exposed and comparison groups were matched on birth weight, race, education, and health insurance. At ages 3, 5, and 7.5 years, 339 children (171 exposed) were assessed for behavior problems by using the Child Behavior Checklist. Generalized estimating equations were used to determine the effects of prenatal methamphetamine exposure, age, and the interaction of exposure and age on behavior problems. Caregiver psychological symptoms were assessed by using the Brief Symptom Inventory. Analyses adjusted for covariates revealed that relative to age 3, children at 5 years had less externalizing and aggressive behavior and more internalizing behavior, somatic complaints, and withdrawn behavior. By age 7.5, aggressive behavior continued to decrease, attention problems increased and withdrawn behavior decreased. There were no main effects for methamphetamine exposure and no interactions of exposure and age. Caregiver psychological symptoms predicted all behavior problems and the quality of the home predicted externalizing problems and externalizing syndrome scores. Behavioral effects longitudinally from ages 3 to 7.5 years were not associated with prenatal methamphetamine exposure, whereas caregiver psychological symptoms and the quality of the home were predictors of behavior problems.

Glial cell diversity and methamphetamine-induced neuroinflammation in human cerebral organoids

Methamphetamine (METH) is a potent stimulant that induces a euphoric state but also causes cognitive impairment, neurotoxicity and neurodevelopmental deficits. Yet, the molecular mechanisms by which METH causes neurodevelopmental defects have remained elusive. Here we utilized human cerebral organoids and single-cell RNA sequencing (scRNA-seq) to study the effects of prenatal METH exposure on fetal brain development. We analyzed 20,758 cells from eight untreated and six METH-treated cerebral organoids and found that the organoids developed from embryonic stem cells contained a diverse array of glial and neuronal cell types. We further identified transcriptionally distinct populations of astrocytes and oligodendrocytes within cerebral organoids. Treatment of organoids with METH-induced marked changes in transcription in multiple cell types, including astrocytes and neural progenitor cells. METH also elicited novel astrocyte-specific gene expression networks regulating responses to cytokines, and inflammasome. Moreover, upregulation of immediate early genes, complement factors, apoptosis, and immune response genes suggests a neuroinflammatory program induced by METH regulating neural stem cell proliferation, differentiation, and cell death. Finally, we observed marked METH-induced changes in neuroinflammatory and cytokine gene expression at the RNA and protein levels. Our data suggest that human cerebral organoids represent a model system to study drug-induced neuroinflammation at single-cell resolution.

Structural brain network development in children following prenatal methamphetamine exposure.

Brain imaging studies in children with prenatal methamphetamine exposure (PME) suggest structural and functional alterations of striatal, frontal, parietal, and limbic regions. However, no longitudinal studies have investigated changes in structural connectivity during the first 2 years of formal schooling. The aim of this study was to explore the effects of PME on structural connectivity of brain networks in children over the critical first 2 years of formal schooling when foundational learning takes place. Networks are expected to gradually increase in global connectedness while segregating into defined systems. Graph theoretical analysis was used to investigate changes in structural connectivity at age 6 and 8 years in children with and without PME. While healthy control children showed increased connectivity in frontal and limbic hubs over time, children with PME showed increased connectivity in the superior parietal cortex and striatum in their global network. Furthermore, compared to control children, those with PME were characterized by less change in segregation of structural networks over time. These findings are consistent with previous work on regions implicated in children with PME, but they additionally demonstrate alterations in structural connectivity between regions that underlie primary cognitive, behavioral, and emotional development. Understanding patterns of network development during critical periods in at-risk children may inform strategies for supporting this group of children in these developmental tasks important for lifelong brain health and development.

Review of long-term consequences of maternal methamphetamine exposure.

Methamphetamine is one of the most abused hard drugs in the Czech Republic. Its popularity is high not only in Eastern Bloc of Europe but is growing in other countries around the world, including the United States. In addition, methamphetamine abuse increases in drug addicts during pregnancy. Although research into the long-term effects of prenatal methamphetamine exposure has been ongoing for many years, the exact mechanism of action and factors that may influence the effect of this drug are still not fully understood. There have been many studies that investigated the effects of addictive substances on the behavior and cognitive function of individuals during adolescence. Some studies have shown prenatal or perinatal influences, e.g. drugs, stress, hypoxia, and malnutrition, can affect drug sensitivity or drug-seeking behavior in adulthood. However, when these factors are most impactful, i.e. prenatal vs. perinatal, and which stages of the prenatal and perinatal periods are the most sensitive to these factors is not yet clear. Our laboratory specializes in research on the effects of drugs (especially methamphetamine) on rat mothers and their offspring during postnatal development, adolescence, and adulthood. This review summarizes our past results on the long-term effects of methamphetamine on the mother and her offspring, its mechanism of action, the role of maternal care, the possible emergence of long-term sensitization, and the critical neurodevelopmental periods for methamphetamine exposure.

Effects of prenatal methamphetamine exposure on neurobehavioral functions in adolescent and adult mice

Effects of prenatal methamphetamine exposure on neurobehavioral functions in adolescent and adult mice

Neurocognitive and neurodevelopmental impact of prenatal methamphetamine exposure: A comparison study of prenatally exposed children with nonexposed ADHD peers

ABSTRACTPrenatal methamphetamine exposure has become an increasingly pervasive concern, especially in rural-based populations and populations of lower socioeconomic status. While research has begun to highlight the effects of prenatal methamphetamine exposure, the long-term impact of this exposure remains an under-investigated topic. This study attempts to investigate the neurocognitive and neurodevelopmental effects of prenatal methamphetamine exposure by comparing the index and full-scale IQ scores on the WISC-IV between a sample of clinically referred children prenatally exposed to methamphetamine (N = 80) and a sample of clinically referred nonexposed children diagnosed with ADHD (N = 44). Children prenatally exposed to methamphetamine showed significantly lower scores on all WISC-IV domains when compared to peers with ADHD. When taking into account polysubstance exposure to alcohol, these differences remained statistically significant, with the exception of the Processing Speed Index (PSI); children reported to have been prenatally exposed to methamphetamine and to alcohol (PME) remained below ADHD peers on all other WISC-IV index scores. Within the prenatally exposed sample, regression analyses indicated that age was a significant negative predictor of PSI scores. Overall findings suggest that prenatal methamphetamine exposure is associated with a notable cognitive impact independent of polysubstance exposure to alcohol, and that the impact of this exposure on processing speed skills may become more pronounced with age.

Cognitive outcomes in prenatal methamphetamine exposed children aged six to seven years

BackgroundMethamphetamine use among pregnant women has become a significant problem. Research delineating the cognitive outcomes of prenatal methamphetamine exposure (PME) in early childhood is limited, however. The aim of this study was to examine effects of PME on cognition in six-to-seven-year-old children. MethodsPME children (n=23) and unexposed controls (n=22) completed a battery of neurocognitive tests, which included the Kaufman Assessment Battery for Children, Boston Naming Test, Beery Developmental Test of Visual-Motor Integration, and Grooved Pegboard Test. ResultsIndependent samples t-tests revealed that PME children scored significantly worse than controls on the measures of IQ, learning and memory, confrontation naming, visual-motor integration, and fine motor coordination. Hierarchical regression analyses that included potential confounding sociodemographic, co-exposure and anthropometric variables confirmed that PME impacts negatively on cognitive performance. ConclusionsThe study confirms that PME has deleterious effects on cognition in several broad cognitive domains, likely by altering underlying brain circuitry in development. These effects may be particularly pronounced at the time when children enter formal schooling. Extended follow-ups into late childhood might help elucidate the developmental trajectory of cognitive dysfunction in PME, and subsequent effects on everyday functioning.

Effect of Prenatal Methamphetamine Exposure on Blood Pressure and Vascular Function in Adult Male and Female Offspring

Hypertension and endothelial dysfunction are commonly associated with cardiovascular disease. Methamphetamine (meth) use is a widespread societal problem, with ~4.7% of the US population having tried meth at least once. Meth use during pregnancy can have deleterious developmental and behavioral consequences for offspring, including delayed development of gross motor skills and decreased memory. Although prenatal meth exposure reportedly causes increased cardiac ischemia in females, there exists very little additional data on the cardiovascular consequences of prenatal meth exposure in adult offspring. The aims of this study were to therefore test whether prenatal meth exposure increases blood pressure and impairs endothelial function in adult offspring, and whether this is influenced by gender. Pregnant female Sprague Dawley rats (8 wk old) were treated with either saline or methamphetamine (5 mg/kg/d sc, once daily) from gestational day 1 until pups were born. Male and female pups were weaned at 3 weeks of age and blood pressure (using tail cuff plethysmography) and vascular function (using myography) assessed after rats were 8 weeks old. Systolic blood pressure (SBP) was increased in male offspring prenatally exposed to meth (SBP = 151±2 mmHg, n=11) vs saline (141±3 mmHg, n=11, P<0.05 vs meth). SBP was similar in female offspring prenatally exposed to meth (SBP = 128±5 mmHg, n=7) and saline (SBP = 125±4 mmHg, n=8, P>0.05 vs meth). In males, endothelium‐dependent relaxation (assessed via relaxation responses to acetylcholine [ACh]) in second‐order mesenteric resistance arteries was impaired by prenatal meth exposure (pEC50: meth‐exposed = −7.5±0.06, n=5; saline‐exposed = −8.0±0.1, n=6; P<0.05). Prenatal meth exposure had no effect on responses to ACh in females (pEC50: meth‐exposed = −7.8±0.05, n=5; saline‐exposed = −8.1±0.08, n=5; P>0.05). Vasorelaxation responses to the endothelium‐independent agonist DEA NONOate, and phenylephrine‐induced vasoconstriction were not influenced by prenatal meth exposure in either gender. These data suggest that prenatal exposure to methamphetamine increases blood pressure and causes endothelial dysfunction in adult male offspring, whereas female offspring prenatally exposed to methamphetamine are protected against an increase in blood pressure and endothelial dysfunction. Prenatal methamphetamine exposure may therefore increase risk of cardiovascular disease in males.Support or Funding InformationRaabe College of Pharmacy, Ohio Northern University

Methamphetamine Consumption during Pregnancy – Effects on Child Health

Methamphetamine abuse during pregnancy represents an emerging health care problem. The consequences are not only of relevance to the pregnant women, but also their unborn child. It is associated with an increased risk of preeclampsia and hypertension, fetal demise, preterm delivery, and intrauterine growth restriction. The deleterious effects of prenatal methamphetamine exposure on the developing fetal brain may lead to long-term neuro-developmental and behavioral problems.Given the current evidence, abuse of methamphetamine during pregnancy must be of utmost concern to health care professionals and to policy-makers. As it has been described for neonatal abstinence syndrome, a multi-professional team is required to improve care of affected women and families. A multi-disciplinary approach is needed, including good prenatal care of pregnant women, perinatal care by specialized obstetricians and neonatologists, and psychiatric treatment by an addiction specialist. Furthermore, families should be integrated into appropriate social support networks.For the development of a structured support program for pregnant women with methamphetamine consumption, methamphetamine use disorder should be considered as a disease that requires medical treatment as well as psychological and social support. The pregnancy should be considered as a window of opportunity to provide the required help.

The effect of prenatal methamphetamine exposure on recognition memory in adult rats.

The use of methamphetamine (MA) among pregnant women is an increasing world-wide health problem. Prenatal MA exposure may cause changes in foetus but the exact effects have remained unclear. The aim of this study is to present the effect of prenatal MA exposure on recognition memory in adult rats. Adult female Wistar rats were injected daily with D-methamphetamine HCl (MA; 5 mg/kg, s.c.) during the entire gestation period. Control females were treated with saline in the same regime. Adult male offspring was administrated acutely by MA (1 mg/kg i.p.) or saline 30 minutes before beginning of an experiment. For testing recognition memory two tasks were chosen: Novel Object Recognition Test (NORT) and Object Location Test (OLT). Our results demonstrate that prenatally MA-exposed animals were worse in NORT independently on an acute administration of MA in adulthood. Prenatally MA-exposed rats did not deteriorate in OLT, but after acute administration of MA in adulthood, there was significant worsening compared to appropriate control. Prenatally saline-exposed offspring did not deteriorate in any test even after acute administration of MA. Our data suggest that prenatal MA exposure in rats cause impairment in recognition memory in adult offspring, but not in spatial memory. In addition, acute administration of MA to controls did not deteriorate either recognition or spatial memory.

Prenatal methamphetamine exposure induces long-lasting alterations in memory and development of NMDA receptors in the hippocampus.

Since close relationship was shown between drug addiction and memory formation, the aim of the present study was to investigate the effects of interaction between prenatal methamphetamine (MA) exposure and MA treatment in adulthood on spatial and non-spatial memory and on the structure of the N-methyl-D-aspartate (NMDA) receptors in the hippocampus. Adult male rats prenatally exposed to MA (5 mg/kg) or saline were tested in adulthood. Non-spatial memory was examined in the Object Recognition Test (ORT) and spatial memory in the Object Location Test (OLT) and in the Memory Retention Test (MRT) conducted in the Morris Water Maze (MWM), respectively. Based on the type of the memory test animals were injected either acutely (ORT, OLT) or long-term (MWM) with MA (1 mg/kg). After each testing, animals were sacrificed and brains were removed. The hippocampus was then examined in Western Blot analysis for occurrence of different NMDA receptors' subtypes. Our results demonstrated that prenatal MA exposure affects the development of the NMDA receptors in the hippocampus that might correspond with improvement of spatial memory tested in adulthood in the MWM. On the other hand, the effect of prenatal MA exposure on non-spatial memory examined in the ORT was the opposite. In addition, we showed that the effect of MA administration in adulthood on NMDA receptors is influenced by prenatal MA exposure, which seems to correlate with the spatial memory examined in the OLT.