Charles Vorhees

....

..Extensive GSL storage occurs in various central nervous system regions in mammalian prosaposin deficiencies...

..In order to compare MA's effects with stress, animals were subjected to a forced swim test in a temporal pattern similar to MA administration [i.e., (30 min/session) 4 times at 2 h intervals]...

..However, since no effects on egocentric learning were found, but were apparent after PD 11-20 treatment, the results show that these 2 forms of learning have different exposure-duration sensitivities...

..No MDMA effects on the Barnes maze were found regardless of test order, however, the interpretation of this finding was compromised by the poor performance of the animals on this task...

..Given that FEN selectively and MDMA preferentially affect serotonin whereas AMPH selectively and MA preferentially affect DA, the data suggest that egocentric learning may be predominantly dopaminergically mediated...

..Cognitive deficits from neonatal MA treatment are associated with the SHRP and may be the product of hypothalamic-pituitary-adrenal (HPA) axis dysregulation during critical periods of brain development...

..Dose distribution warrants greater attention in the design of developmental drug studies along with the standard considerations of dose and age...

..The results demonstrate that a narrower exposure window (5 days) changes the long-term effects of MA treatment compared to longer exposures (10 days)...

..Whether selective serotonin reuptake inhibitors (SSRIs) exposure during adolescent brain development causes lasting effects remains unresolved...

..We present protocols for performing variants of the MWM test, from which results can be obtained from individual animals in as few as 6 days...

..The data suggest that caution is warranted concerning the developmental efficacy of quinpirole...

..P41-50 is the periadolescent stage of brain development in rodents. The effects observed at this age may suggest a previously unrecognized period of susceptibility for MA-induced cognitive deficits...

..Correlational analyses suggested that the MWM reversal interaction involves multiple monoamine changes. The results indicate that developmental MDMA exposure can interact with adult exposure to interfere with some aspects of learning...

..The large litter approach offers a novel method to control for undernutrition during the preweaning period in rodents...

....

..Taken together, this suggests that a potential mechanism for the sequential learning deficits in FEN-treated animals is a result of prolonged increases in CORT output...

..Methamphetamine (MA) has been implicated in cognitive deficits in humans after chronic use. Animal models of neurotoxic MA exposure reveal persistent damage to monoaminergic systems but few associated cognitive effects...

..The results demonstrate that neonatal MA treatment induces spatial learning and reference memory deficits that emerge early and persist until at least 1 year of age, suggesting permanence...

....

..We previously developed a method to attenuate MA-induced corticosterone release using adrenal autotransplantation (ADXA) in neonatal rats. This exposure period corresponds to the second-half of human pregnancy...

..We examined the effects of neonatal isoflurane exposure and blood glucose on brain cell viability, spontaneous locomotor activity, as well as spatial learning and memory in mice...

..Recently, the club drug 5-methoxy-N,N-diisopropyltryptamine (5-MeO-DIPT) has gained popularity...

....

..Taken together, the data show that a single-day regimen of MDMA induces deficits similar to that of multiple weekly treatments...

..These findings demonstrate that NPSR1 is essential in mediating NPS effects on behavior...

..The data demonstrate that MA-induced learning deficits can be dissociated from drug-induced increases in plasma corticosterone or hyperthermia, but co-occur with dopamine and serotonin reductions...

..The possible relationship between these changes and the long-term cognitive effects of developmental MA administration are discussed...

..The findings indicate that early MA exposure induces hippocampal BDNF increases that precede the later emergence of spatial learning deficits...

..Assessment of path integration may provide a sensitive index of MDMA-induced learning deficits...

..The findings demonstrate that neonatal treatment with MA induces a selective impairment of reference memory-based spatial learning while sparing sequential, cued, and working memory-based learning...

..These data would caution against even casual use of methamphetamine by women during pregnancy since even low doses could alter the ability of the child to learn...

....

..The data indicate that an acute exposure to these drugs alters CORT and glucose levels, raising the possibility that these changes may have effects on behavioral and cognitive function, as we and others have previously demonstrated...

..The method should be applicable to other models of developmental stress/corticosterone release...

..These results support the view that saposin C has multiple roles in glycosphingolipid (GSL) catabolism as well as a prominent function in CNS and axonal integrity independent of its role as an optimizer/stabilizer of GCase...

..However this D2 mechanism does not apply to methamphetamine-induced striatal serotonin reductions...

..In rats, neurotoxic doses of methamphetamine (MA) induce astrogliosis, long lasting monoamine reductions, reuptake transporter down-regulation, and learning impairments...

..Taken together, the evidence shows that MDMA exposure has adverse effects on the developing brain and behavior. The animal and human data on developmental MDMA exposure are reviewed and their public health implications discussed...

..The neurobehavioral changes seen in heterozygous mice suggest that these mouse models may be useful in future investigations of the associated human CNS disorders...

..Corticosterone levels were shown to be elevated during the behavioral testing period in animals exposed to FEN...

..Although the monoamine changes are transient, they may alter developing neural circuits sufficiently to permanently disrupt later learning and memory abilities...

..CONCLUSION: The data suggest that the spatial learning and memory deficits induced by MDMA are long lasting, while the path integration deficits recover over time...

..The model introduced here may be useful for investigating the interaction of Pb and chronic developmental stress...

..Manipulating the aberrant apoptosis-associated DNA synthesis that occurs with hypoxia-ischemia and perhaps neurodegenerative diseases could promote neuronal survival and neurogenesis...

..The authors used these agents in a delayed preconditioning model to test the hypothesis that they could provide neuroprotection against neonatal hypoxia-ischemia as assessed by a battery of behavioral tests...

..Together, our observations indicate an important role for Npas3 in controlling normal brain development and neurosignaling pathways...

....

..The data suggest a potential cause for the learning and memory deficits induced by neonatal MA exposure; however, the underlying mechanism that produces these neuronal changes is unknown...

..The data suggest that PTPalpha serves a regulatory function in learning and other forms of neuroplasticity...

..This study was designed to assess the relationships between the duration of hypoxia-ischemia (HI) on P10 and the structural and functional neurological deficits that appear in the adult mouse as a consequence...

..5-MEO-DIPT may have the potential to induce untoward effects in humans...

..The data demonstrate that (+)-methamphetamine is a robust activator of corticosterone release in developing animals and this release is extensively modified by age and previous drug exposure...

..The absence of functional MT-I,II proteins does not result in significantly worse injury following 45 min of HI on P10. The MT-I,II deficient mice have baseline impairments in spatial learning but not retention...

..We investigated the long-term effects of delayed preconditioning with Iso, hypoxia, or room air on motor and cognitive function in mice that had 65 min of hypoxia-ischemia on postnatal day 10...

..This study would also provide guidelines for the experimental designs of behavioral evaluation on innovative therapies for the treatment of MPS type I...

..These data suggest that sensorimotor deficits do not account for the spatial learning and memory deficits in animals exposed neonatally to MA...

..Ubiquitous CrT knockout mice have learning and memory deficits resembling human CrT deficiency and this model should be useful in understanding this disorder...

....

..B-/- provide a useful model for understanding the contributions of this saposin to GSL metabolism and homeostasis...

..We find that the haploinsufficiency of both alpha2 and alpha 3 isoforms result in behavioral defects...

..Our results suggest that hippocampal c-fos expression is not essential for spatial learning...

..These results suggest that a lack of DFF45 facilitates hippocampus-dependent nonspatial memory, as well as hippocampus-dependent spatial memory...

..Together, these results suggest that ischemia-hypoxia is a powerful stimulus for spontaneous coagulation leading to reperfusion deficits and autophagic/lysosomal cell death in brain...

..Although dioxin in utero is well known to cause AHR-dependent cleft palate and hydronephrosis, cHBB did not; thus, chronic activation of the AHR appears to be necessary but not sufficient for AHR-mediated teratogenicity...

..The ability of METH to cause long-term reductions in PKA activity may partially account for some of behavioral deficits exhibited by rats exposed to METH prior to weaning...

..These data indicate that early MDMA exposure has long-term effects on the 5-HT and DA neurotransmitter systems that may be mediated, at least partially, by changes in 5-HT1A receptor sensitivity...

..Although the data do not suggest a mechanism for the learning deficits, they indicate that pharmacokinetic differences may contribute to the effects seen when exposure is begun on P11...

....

..The number of prenatally MA exposed children continues to grow. Our goal is to develop models of early MA exposure that permit an understanding of the long-term consequences on brain development and cognition. ..

..This application represents a continuation of the strengths of the program from the past and adds new initiatives that will move teratology training to the next level in understanding the mechanisms of abnormal development ..

..The number of prenatally MA exposed children continues to grow. Our goal is to develop models of early MA exposure that permit an understanding of the long-term consequences on brain development and cognition. ..

..abstract_text> ..

..Such data will help identify risks associated with the prenatal use of MDMA on brain and cognitive development. ..

..A future goal is to compare the developmental effects of methamphetamine to that of related drugs...

....