Impulse control disorders in Parkinson disease: A cross-sectional study in Morocco.

Impulse control disorders (ICDs) in Parkinson's disease (PD) comprise a class of psycho-behavioral disorders often associated with dopamine agonist treatment. The aim of our study was to determine the prevalence of ICDs in a group of Moroccan PD patients and to bring forward some specific aspects in our population. One hundred twenty-five PD patients, without memory impairment and treated for at least six months, were studied. They were questioned about ICDs using the QUIP-RS, and simultaneously evaluated on the motor symptoms and their treatment. Our sample was then divided into two groups: ICDs (+) and ICDs (-) groups. ICDs were identified in 28% of patients: pathological gambling in 3.2%, compulsive sexual behavior in 7.2%, pathological buying in 9.6%, eating behavior disorder in 7.2%, punding-hobbyism in 11.1%. At least two ICDs were found in 14% of patients and dopamine dysregulation syndrome in 10.4%. We also noticed another kind of "ICDs-mimics" specific to our own social context such as "excessive charity" in 18.4%, or excessive reading of the Qur'an in 9.6%. These aspects were not included in the calculation of ICDs prevalence. The ICDs (+) group was younger than the ICDs (-) group (P=0.042) and ICDs were more frequent in men (P=0.031). Dopamine agonist equivalent daily dose (DAED) was significantly higher (P=0.01) in the ICDs (+) group. There are no differences between classes of dopamine agonist used. Young age, male gender and DAED are risk factors for the occurrence of ICDs in Moroccan PD patients, as already described in the DOMINION cohort, but the prevalence found in our study was higher. We highlighted some specific ICDs-mimics in our Arab-Muslim population.

Association of inflammatory cytokine gene polymorphisms with inflammatory bowel disease in a Moroccan cohort.

The purpose of this study was to investigate whether common variants in inflammatory and immune response genes influence inflammatory bowel disease (IBD) risk among Moroccan patients. Using a candidate gene approach, 10 single-nucleotide polymorphisms mapping on six genes (MIF_rs755622, TNFA_rs1800629, IL6_rs2069840, IL6R_rs2228145, IL6ST_rs2228044, IL17A (rs2275913, rs4711998, rs7747909, rs8193036, rs3819024)) were assessed in 510 subjects grouped in 199 IBD and 311 healthy controls. Genotyping was performed with the TaqMan allelic discrimination technology. The results were analyzed using PLINK software. The frequency of allele A for TNFA rs1800629 was significantly higher in ulcerative colitis (UC) patients compared with controls (30.16 vs 16.72%; P=0.0005; odds ratio (OR)=2.15; 95% confidence interval (CI)=1.39-3.32). Statistically significant association to UC was also found under dominant AA+AG vs GG (OR=1.85, 95% CI=1.07-3.21; P=0.02) and recessive models (OR=8.38; 95% CI=2.86-24.53; P=0.0001). In the same way, an association of TNFA rs1800629 variant was observed with IBD under recessive model AA vs AG+GG (OR=4.10; 95% CI=1.56-10.76; P=0.004). No evidence of significant associations was found for the remaining investigated polymorphisms. Our data suggest that TNFA gene promoter polymorphism participates in determining IBD susceptibility in Moroccan patients.

Quantitative real-time polymerase chain reaction as an efficient molecular tool for detecting minimal residual disease in Moroccan chronic myeloid leukemia patients.

Chronic myeloid leukemia (CML) is characterized by BCR-ABL translocation and an increased number and migration of immature myeloid cells into the peripheral blood. The detection limit of the BCR-ABL transcript, particularly after treatment, is controversial. In the present study, we used quantitative real-time reverse transcription-polymerase chain reaction (RT-qPCR) to monitor BCR-ABL expression in Moroccan CML patients undergoing imatinib treatment, and compared the results with those of conventional PCR and fluorescence in situ hybridization (FISH). The aim of this study was to establish a new molecular tool for in vitro diagnosis of CML. In a retrospective comparative analysis, 20 CML Moroccan patients who had received imatinib treatment (N = 20) were analyzed by real-time PCR, conventional RT-PCR, and FISH. Half of the samples analyzed (N = 10) were positive for BCR-ABL gene expression, while the other half (N = 10) were negative according to conventional PCR. Interestingly, 5 of the 10 samples shown to be negative by conventional PCR showed positive expression of the BCR-ABL gene according to RT-qPCR. The RT-qPCR results were confirmed by FISH, which revealed a high concordance (100%) rate. We found that real-time RT-qPCR is more reliable and should be used in Moroccan biomedical analysis laboratories to monitor CML progression, particularly for minimal residual disease, following imatinib treatment.

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and Alzheimer's disease.

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a ubiquitous enzyme that catalyzes the sixth step of glycolysis and thus, serves to break down glucose for energy production. Beyond the traditional aerobic metabolism of glucose, recent studies have highlighted additional roles played by GAPDH in non-metabolic processes, such as control of gene expression and redox post-translational modifications. Neuroproteomics have revealed high affinity interactions between GAPDH and Alzheimer's disease-associated proteins, including the ß-amyloid, ß-amyloid precursor protein and tau. This neuronal protein interaction may lead to impairment of the GAPDH glycolytic function in Alzheimer's disease and may be a forerunner of its participation in apoptosis. The present review examines the crucial implication of GAPDH in neurodegenerative processes and clarifies its role in apoptotic cell death.

[Clinical presentation of Moroccan cases with Alzheimer's disease]. / Présentation clinique de cas marocains atteints de la maladie d'Alzheimer.

INTRODUCTION: The diagnostic approach for Alzheimer's disease is based on the presence of cerebral atrophy combined with the score of the mini-examination of the mental state. In this context, this study was conducted to assess the correlation between imaging and neuropsychological testing for cases of early-onset and late-onset Alzheimer's disease. AIM OF THE STUDY: Analysis of the clinical and paraclinical aspects of Moroccan cases with Alzheimer's disease. METHODS: Seventeen sporadic cases and 8 family cases were seen at the memory clinic of the Neurology Department of the University of Casablanca Ibn Rochd Hospital. A family history was obtained through a clinical interview of the patient and a yes or no self-reporting questionnaire from the guardian or other family member. The disease was considered familial if at least one additional first degree relative suffered from early-onset AD-type dementia. All patients underwent standard somatic neurological examination, cognitive function assessment, brain imaging and laboratory tests. Written consent was obtained from the patients and their guardians prior to the study. RESULTS: In our study of 25 individuals, the observed mean age of AD patients was 64.52 ± 9.30 and we observed a slight female predominance (56% versus 44%). In addition, we found a prevalence of AD of approximately 20%, increasing with age, in the population below 60 years of age. Approximately half of our patients (48%) had a score lower than 10 and were affected by severe insanity, while 28% were affected by moderate severe insanity and 24% were light to moderately insane. Twenty-five patients underwent neuroimaging, 18 of whom were assessed by MRI, while 7 were assessed by CT. All patients had hippocampal atrophy, which progressed to affect others brain regions. The blood tests showed no abnormalities in the 25 enrolled AD cases. DISCUSSION: Age is undoubtedly the main risk factor for AD; this is also the true for our cases where advanced age was responsible for the exponential increase of the disease's frequency; it reached a peak in the age group of 60-69 years. The AD diagnosis approach is based on the presence of cerebral atrophy combined with the score of the mini-examination of the mental state (MMSE). In our study, in addition to the MMSE, depending on the level of education, the clinician used other tests that do not necessarily require a level of education such as the BEC96, visual short-term or digital memory assessment, work memory assessment, language assessment test (DO80) and apraxia. Neuropsychological examination of the cases with a score of less than 10 showed severe cognitive impairment. The cases presented memory and language impairments, aphasia, visual spatial disorientation, decreased autonomy, executive dysfunction and praxis deficits, all major causes of severe dementia. Neuroimaging revealed hippocampal and cortical atrophy. Correlated with the other studies that aimed to establish links between brain alterations and neuropsychological disorders, we can conclude that a higher level of atrophy reflects a decrease in neuropsychological performance.

[Genetic aspects of Alzheimer's disease (Review)]. / Les aspects génétiques de la maladie d'Alzheimer (Revue).

Alzheimer's disease is a degenerative brain disorder, which concerns memory, cognition and behavior pattern. Its etiology is unknown, it is characterized by typical histological lesions: senile plaques and neuro-fibrillary tangles. Alzheimer's disease is a multifactorial pathology, characterized by interactions between genetic and environmental factors. Genetic factors concern first of all the exceptional monogenic forms, characterized by early onset (<60 years), autosomal dominant forms. Mutations of the genes coding for amyloid-ß precursor protein or preselinins 1 and 2 are involved. The much more frequent sporadic forms also have genetic factors, the best studied being the apolipoprotein E4 coding allele and some more recent genotypes which will be mentioned. No causal, only symptomatic treatments are available.

Colorectal cancer: comparison of clinicopathologic features between Moroccans patients less than 50 years old and older.

INTRODUCTION: Colorectal cancer is a major public health problem. However, this cancer is usually developed on preexisting lesion. This makes this cancer accessible to a prevention strategy. OBJECTIVE: The aim of this study was to determine the clinicopathologic characteristics of patients under 50 years. PATIENTS AND METHODS: This study involved 133 patients with colorectal cancer recruited in CHU Ibn-Rochd, Casablanca. Data relating age, sex, stage at presentation, histological type and tumor location were obtained from the pathological and clinical records of each patient. Statistical analysis was performed to compare clinicopathological data in patients under 50 years and in older patients. RESULTS AND DISCUSSION: The average age of patients was 54 years. The frequency of patients aged 50 or under was 40.6% The tumors in the youngest age group were more often mucinous and signet ring cells (18.5%) versus (5.1%) in the oldest age group. The right colon was more often affected in the youngest age group, 38.9% versus 17.7% in the oldest age group (P=0.008). CONCLUSION: The proposition of colorectal cancer in subjects 50 or under was high in Morocco. Colorectal cancers in the youngest age group were more often mucinous or signet ring cells and was more often located in the right colon. We intend to complete this study by a genetic study to help improve prevention and care of young patient.

Effect of different genetics variants: CYP2C9*2, CYP2C9*3 of cytochrome P-450 CYP2C9 and 1639G>A of the VKORC1 gene; On acenocoumarol requirement in Moroccan patients.

Coumarin derivatives such as acenocoumarol represent the therapy of choice for the long-term treatment and prevention of thromboembolic diseases. Many genetics determinants involved in the metabolism of acenocoumarol have been shown to influence the anticoagulant dosage. The aim of this work was to evaluate, for the first time in Maghreb, the allelic frequencies of CYP2C9*2, CYP2C9*3 and VKORC1 -1639G>A mutations, and to establish the role of this polymorphisms in modulating the acenocoumarol requirement in Moroccan patients receiving anticoagulation treatment. Three groups of patients, with low, medium, or high acenocoumarol dose requirements were studied. Genetic analyses of VKORC1 -1639G>A, CYP2C9*2, and CYP2C9*3, were performed in 114 Moroccan patients with stable acenocoumarol dose. The results showed that the allelic frequencies of the three mutations studied was varies, most of patients having CYP2C9*2 and CYP2C9*3 mutations belong to a group with low dose of acenocoumarol, with P-value of 0.0082 and the single patient with CYP2C9*3 on homozygous form belongs to the same group and carried the A allele for VKORC1 gene. In conclusion, the present study confirmed the large interindividual variability in acenocoumarol maintenance dose due to CYP2C9*2, CYP2C9*3 and VKORC1 -1639G>A polymorphisms, and demonstrated that these alleles modulates sensitivity to acenocoumarol, a finding indicating that a reduced initial loading dose of acenocoumarol should be used in carriers of this allele, also, she indicates the usefulness of predictive testing concerning these mutations when an hypocoagulability is installed and not explained by the dose of VKA.

[Potential role of the angiogenic factor "EG-VEGF" in gestational trophoblastic diseases]. / Rôle potentiel du facteur angiogénique «EG-VEGF¼ dans les maladies gestationnelles trophoblastiques.

Gestational trophoblastic disease (MGT) includes a wide spectrum of pathologies of the placenta, ranging from benign precancerous lesions, with gestational trophoblastic tumors. Metastases are the leading causes of death as a result of this tumor. They represent a major problem for obstetrics and for the public health system. To date, there is no predictor of the progression of molar pregnancies to gestational trophoblastic tumor (GTT). Only an unfavorable plasma hCG monitoring after evacuation of hydatidiform mole is used to diagnose a TTG. The causes of the development of this cancer are still poorly understood. Increasing data in the literature suggests a close association between the development of this tumor and poor placental vascularization during the first trimester of pregnancy. The development of the human placenta depends on a coordination between the trophoblast and endothelial cells. A disruption in the expression of angiogenic factors could contribute to uterine or extra-uterine tissue invasion by extravillous trophoblast, contributing to the development of TTG. This review sheds lights on the phenomenon of angiogenesis during normal and abnormal placentation, especially during the MGT and reports preliminary finding concerning, the variability of expression of "Endocrine Gland-Derived Vascular Endothelial Growth Factor" (EG-VEGF), a specific placental angiogenic factor, in normal and molar placentas, and the potential role of differentiated expressions of the main placental angiogenic factors in the scalability of hydatidiform moles towards a recovery or towards the development of gestational trophoblastic tumor. Deciphering the mechanisms by which the angiogenic factor influences these processes will help understand the pathophysiology of MGT and to create opportunities for early diagnosis and treatment of the latter.

Influence of genetics and non-genetic factors on acenocoumarol maintenance dose requirement in Moroccan patients.

WHAT IS KNOWN AND OBJECTIVE: Coumarin derivatives such as acenocoumarol represent the therapy of choice for the long-term treatment and prevention of thromboembolic diseases. Many genetic, clinical and demographic factors have been shown to influence the anticoagulant dosage. Our aim was to investigate the contribution of genetic and non-genetic factors to variability in response to acenocoumarol in Moroccan patients. METHODS: Our study included 114 adult Moroccan patients, receiving long-term acenocoumarol therapy for various indications. Tests for VKORC1 -1639G>A promoter polymorphism (rs9923231), CYP2C9*2 rs1799853, CYP2C9*3 rs1057910, and CYP4F2 rs2108622 alleles were undertaken using Taq Man(®) Pre-Developed Assay Reagents for allelic discrimination. The statistical analysis was performed using the SAS V9 statistical package. RESULTS AND DISCUSSION: Genotyping showed that the allele frequencies for the SNPs studied were no different to those found in Caucasians population. A significant association was observed between the weekly maintenance dose and the VKORC1 (P = 0·0027) and CYP2C9 variant genotypes (P = 0·0082). A final multivariate regression model that included the target International Normalized Ratio, VKORC1 and CYP2C9 genotypes explained 36·2% of the overall interindividual variability in acenocoumarol dose requirement. WHAT IS NEW AND CONCLUSION: Our study shows large interindividual variability in acenocoumarol maintenance dose requirement in our population. VKORC1 and CYP2C9 variants significantly affected acenocoumarol dose, in-line with results in other populations. For the Moroccan population, the SNPs that have the largest effect on acecoumarol dose are CYP2C9 rs1799853, CYP2C9 rs1057910 and VKORC1 rs9923231.

Methylenehydrofolate reductase (C677T) polymorphism and large artery ischemic stroke subtypes.

BACKGROUND: The role for the methylenetetrahydrofolate reductase C677T gene variants in the risk of ischemic stroke is controversial. METHOD: This first case-control study including 91 cases affected by ischemic stroke and 182 controls matched for age, sex, and same area was conducted in Casablanca, Morocco. Allele and genotype frequency were characterized by using PCR followed by HinfI enzymatic digestion. RESULTS: We found no statistic association of T allele carriers genetic factors with stroke; odds ratio, 1.1; 95% confidence interval (CI), 0.59-2.04, P = 0.303. The results shown significant association of T allele carriers genetic factors with atherothrombotic subtype stroke (n = 42); odds ratio, 2.1; 95% CI: 1.17-3.8; P = 0.012, and adjusted odds ratio of 6.5; 95% CI: 1.86-23.1, P = 0.003, for TT genotype variant compared with CC wild genotype. CONCLUSION: We suggested that MTHFR C677T variant may be a determinant of atherothrombotic event of ischemic stroke in Morocco.

JAK2-V617F mutation in Moroccan patients with myeloproliferative disorders: contribution, diagnosis and therapeutic prospects.

AIMS: The JAK2 V617F is a recent discovery. The implication of this mutation in the pathogenesis of the myeloproliferative disorders (MPDs) is currently confirmed. Our study is the first to be interested in the status of the JAK2 V617F mutation among myeloproliferative disorders patients in Morocco. PATIENTS AND METHODS: Our study focused on 70 non-CML MPD patients, attending several departments of hematology and internal medicine across Morocco. The mutation was detected by allele-specific PCR (AS-PCR). RESULTS: The V617F JAK2 mutation incidence in polycythemia vera, essential thrombocythemia and idiopathic myelofibrosis are respectively 89.47%, 62.5% and 33.33%. The V617F JAK2 mutation was absent within the patients with secondary erythrocytosis or thrombocytosis. We also found that the patients carrying the mutation displayed a leucocytosis and higher levels of haemoglobin and hematocrit than mutation-negative patients. CONCLUSION: Our study is the first to assess the status of the JAK2 V617F mutation in patients with MPDs in Morocco. However, our data seem to confirm that the JAK2 V617F mutation is rather uncommon in myeloid malignancies other than the classical BCR/ABL MPD negative.

[Phenotype-genotype correspondence in spinal muscular atrophy in a Moroccan family]. / Etude de la corrélation génotype-phénotype dans l'amyotrophie spinale infantile (ASI) dans une famille marocaine.

Spinal muscular atrophy (SMA) is an autosomal recessive disorder with a highly variable clinical course and prognosis. We report on the cases of three siblings with SMA. The weakness muscular observes at three siblings but more earlier and severe to the index case with a fast evolution towards respiratory distress syndrome resulting in its death at 5 years. The homozygous deletions of exons 7 and 8 of the telomeric SMN gene were found in all three siblings. No child showed deletion of NAIP gene. Muscular weakness and respiratory distress severity however were different among the siblings. The index patient died at the age of 5 because of respiratory insufficiency. Several molecular mechanisms may be involved in such phenotypic variability. The PCR-RFLP method allows to confirm clinical diagnosis of SMA in children, while avoiding more invasive methods such as EMG and muscular biopsy. However, this diagnostic tool does not allow yet the distinction between different clinical forms of SMA.

ACE insertion/deletion polymorphism is positively associated with resistant hypertension in Morocco.

OBJECTIVE: The aim of the present study was to investigate the association of I/D polymorphisms of ACE gene is associated with resistant hypertension and essential controlled hypertension. RESULTS: Our results show that the homozygous mutant genotype DD was more represented among resistant than controlled (58.1% vs 41.9% respectively), however the homozygote wild was more represented among controlled than resistant (70.6% vs 29.4% respectively). But more heterozygous ID among controlled than resistant patients (63.6% vs 36.4% respectively). The difference was statistically significant (p = 0.04). Analysis of clinical parameters indicated that physical activity contributes to resistant hypertension (P < 0.05). Based on our findings, the homozygous mutant for DD of ACE gene is associated with resistant hypertension in our population. Further studies with larger sample sizes are needed to confirm the results of this study.

Prenatal stress alters diazepam withdrawal syndrome and 5HT1A receptor expression in the raphe nuclei of adult rats.

Early-life events have long-term effects on brain structures and cause behavioral alterations that persist into adulthood. The present experiments were designed to investigate the effects of prenatal stress on diazepam-induced withdrawal syndrome and serotonin-1A (5HT1A) receptor expression in the raphe nuclei of adult offspring. The results of the present study reveal that maternal exposure to chronic footshock stress increased the anxiety-like behavior in the prenatally stressed (PS) animals withdrawn from chronic diazepam (2.5mg/kg/day i.p for 1week). Moreover, prenatal stress induced a down-regulation of 5HT1A mRNA in the raphe nuclei of adult offspring. To our knowledge, this study is the first to demonstrate that maternal exposure to chronic footshock stress enhances diazepam withdrawal symptoms and alters 5HT1A receptor gene expression in the raphe nuclei of adult offspring. Thus, more studies are needed to clarify the mechanisms underlying the decrease of 5HT1A receptors expression in the raphe nuclei of PS rats.

Intra-familial phenotypic variability in a Moroccan family with hearing loss and palmoplantar keratoderma (PPK).

Mutations in the GJB2 gene encoding connexin 26 are the main cause of hereditary hearing impairment. These mutations generate mainly autosomal recessive and rarely autosomal dominant deafness. Dominant mutations in GJB2 can be responsible for isolated deafness as well as syndromic hearing loss associated with various skin abnormalities. Until now few papers discuss dominant mutations in the GJB2 gene. In this work we report a rare case about a Moroccan family with a compound heterozygous mutation (the dominant p.R75Q and the recessive c.35delG alleles) in the GJB2 gene with intra-familial phenotypic variability. This study reinforces the involvement of p.R75Q mutation of GJB2 in syndromic deafness associated with dermatological diseases the palmoplantar keratoderma.

Compound heterozygous SLC29A3 mutation causes H syndrome in a Moroccan patient: A case report.

H syndrome is an autosomal recessive syndrome, which affects the skin and some vital organs, it is caused by mutations in the SLC29A3 gene, encoding the human equilibrative nucleoside transporter hENT3. This report describes a patient with typical features of H syndrome. Based on the patient's clinical features, SLC29A3 was selected for molecular investigation. Through direct sequencing, a compound heterozygous alteration in the SLC29A3 gene was found. The c.243delA frameshift mutation leading to a premature termination, resulting in a truncated protein, and a splice site mutation c.300+1G>C predicted to cause a splicing error. This contribution extends the clinical variability of compound heterozygous SLC29A3 mutations resulting in an additional multisystemic manifestation of the clinical spectrum of SLC29A3 disorders.

Effect of prenatal stress on memory, nicotine withdrawal and 5HT1A expression in raphe nuclei of adult rats.

Maternal distress has often been associated with cognitive deficiencies and drug abuse in rats. This study examined these behavioral effects in offspring of mothers stressed during gestation. To this end, pregnant dams were subjected to daily electric foot shocks during the last 10 days of pregnancy. We measured litter parameters and body weights of the descendants after weaning (21 days) and at adulthood (80 days). Afterwards, prenatally stressed and control rats' performances in the novel object recognition test were compared in order to evaluate their memory while others underwent the Water consumption test to assess the nicotine withdrawal intensity after perinatal manipulations. Meanwhile, another set of rats were sacrificed and 5HT1A receptors' mRNA expression was measured in the raphe nuclei by quantitative Real Time PCR. We noticed no significant influence of maternal stress on litter size and body weight right after weaning. However, control rats were heavier than the stressed rats in adulthood. The results also showed a significant decrease in the recognition score in rats stressed in utero compared to the controls. Moreover, a heightened anxiety symptom was observed in the prenatally stressed offspring following nicotine withdrawal. Additionally, the Real Time PCR method revealed that prenatal stress induced a significant decrease in 5HT1A receptors' levels in the raphe nuclei. Nicotine had a similar effect on these receptors' expression in both nicotine-treated control and prenatally stressed groups. Taken together, these findings suggest that the cognitive functions and drug dependence can be triggered by early adverse events in rats.

Prenatal stress induces vulnerability to nicotine addiction and alters D2 receptors' expression in the nucleus accumbens in adult rats.

Prenatal stress (PS) can induce several long-lasting behavioral and molecular abnormalities in rats. It can also be considered as a risk factor for many psychiatric diseases like schizophrenia, depression or PTSD and predispose to addiction. In this study, we investigated the effect of prenatal stress on the reinforcing properties of nicotine in the CPP paradigm. Then, we examined the mRNA expression of the D2 dopaminergic receptors using the quantitative real-time PCR technique in the nucleus accumbens (NAcc). We found that prenatally stressed rats exhibited a greater place preference for the nicotine-paired compartment than the control rats. Moreover, we observed an overexpression of the DRD2 gene in adult offspring stressed in utero and a downregulation in the PS NIC group (PS rats treated with nicotine) compared with their control counterparts (C NIC). These data suggest that maternal stress can permanently alter the offspring's addictive behavior and D2 receptors' expression.

Long-term effects of prenatal stress and diazepam on D2 receptor expression in the nucleus accumbens of adult rats.

Early life stress during the gestational period alters specific neuronal circuits leading to behavioral alterations later in life. In the present study, we assessed the effects of prenatal stress and repeated benzodiazepine administration on dopamine receptor 2 expression in the nucleus accumbens of adult offspring. Our results show elevated Drd2 expression levels in the nucleus accumbens (NAcc) of prenatally stressed rats compared to control subjects, while repeated diazepam administration in adulthood down-regulated Drd2 expression and prevented the effect of prenatal stress. These observations suggest that prenatal stress may induce permanent alterations in the corticolimbic pathway implicated in drug-seeking behavior.