Potentiation of latent inhibition by haloperidol and clozapine is attenuated in Dopamine D2 receptor (Drd-2) deficient mice: Do antipsychotics influence learning to ignore irrelevant stimuli via both Drd-2 and non-Drd-2 mechanisms?

Whether the dopamine Drd-2 receptor is necessary for the behavioural action of antipsychotic drugs is an important question, as Drd-2 antagonism is responsible for their debilitating motor side effects. Using Drd-2 null mice (Drd2 -/-) it has previously been shown that Drd-2 is not necessary for antipsychotic drugs to reverse D-amphetamine disruption of latent inhibition (LI), a behavioural measure of learning to ignore irrelevant stimuli. Weiner's 'two-headed' model indicates that antipsychotics not only reverse LI disruption, 'disrupted LI', but also potentiate LI when low/absent in controls, 'persistent' LI. We investigated whether antipsychotic drugs haloperidol or clozapine potentiated LI in wild-type controls or Drd2 -/-. Both drugs potentiated LI in wild-type but not in Drd2 -/- mice, suggesting moderation of this effect of antipsychotics in the absence of Drd-2. Haloperidol potentiated LI similarly in both Drd1 -/- and wild-type mice, indicating no such moderation in Drd1 -/-. These data suggest that antipsychotic drugs can have either Drd-2 or non-Drd-2 effects on learning to ignore irrelevant stimuli, depending on how the abnormality is produced. Identification of the non-Drd-2 mechanism may help to identify novel non-Drd2 based therapeutic strategies for psychosis

HIV Subtypes B and C gp120 and Methamphetamine Interaction: Dopaminergic System Implicates Differential Neuronal Toxicity

HIV subtypes or clades differentially induce HIV-associated neurocognitive disorders (HAND) and substance abuse is known to accelerate HIV disease progression. The HIV-1 envelope protein gp120 plays a major role in binding and budding in the central nervous system (CNS) and impacts dopaminergic functions. However, the mechanisms utilized by HIV-1 clades to exert differential effects and the methamphetamine (METH)-associated dopaminergic dysfunction are poorly understood. We hypothesized that clade B and C gp120 structural sequences, modeling based analysis, dopaminergic effect, and METH potentiate neuronal toxicity in astrocytes. We evaluated the effect of clade B and C gp120 and/or METH on the DRD-2, DAT, CaMKs and CREBP transcription. Both the structural sequence and modeling studies demonstrated that clade B gp120 in V1-V4, α -2 and N-glycosylated sites are distinct from clade C gp120. The distinct structure and sequence variation of clade B gp120 differentially impact DRD-2, DAT, CaMK II and CaMK IV mRNA, protein and intracellular expression compared to clade C gp120. However, CREB transcription is upregulated by both clade B and C gp120, and METH co-treatment potentiated these effects. In conclusion, distinct structural sequences of HIV-1 clade B and C gp120 differentially regulate the dopaminergic pathway and METH potentiates neurotoxicity

Data management study, volume 5. Appendix I - Contract or data package overall management /MA/, scheduling /SC/, MANNING and financial /MF/ Final report

Overall management, scheduling, manpower, and financial aspects of Voyager data managemen

Data Management Study, Volume 5. Appendix H - Contractor Data Package Logistics and Support /LS/ Final Report

Contractor data package for Voyager logistics and support in transportation, communications, supply, and maintenanc

Data management study, volume 5. Appendix E - Contractor data package quality assurance /QA/ Final report

Manufacturing verification tests for quality assurance and control data management on Voyager spacecraf

Data management study, volume 5. Appendix F - Contractor data package test /TE/ and mission operations /MP/ Final report

Test and mission operations contractor data package for Voyager spacecraf

On the contribution of demographic change to aggregate poverty measures for the developing world

Recent literature and new data help determine plausible bounds to some key demographic differences between the poor and non-poor in the developing world. The author estimates that selective mortality-whereby poorer people tend to have higher death rates-accounts for 10-30 percent of the developing world's trend rate of"$1 a day"poverty reduction in the 1990s. However, in a neighborhood of plausible estimates, differential fertility-whereby poorer people tend also to have higher birth rates-has had a more than offsetting poverty-increasing effect. The net impact of differential natural population growth represents 10-50 percent of the trend rate of poverty reduction.Health Monitoring&Evaluation,Services&Transfers to Poor,Safety Nets and Transfers,Rural Poverty Reduction,Health Indicators