Methamphetamine-Induced Behavioral and Physiological Effects in Adolescent and Adult HIV-1 Transgenic Rats

Kass, Marley D.; Liu, Xiangqian; Vigorito, Michael; Chang, Linda; Chang, Sulie L.

doi:10.1007/s11481-010-9221-z

Cited by 26 publications

(31 citation statements)

References 39 publications

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“…In methamphetamine-treated rodents, an intra-nigral infusion of 10 μg/μL (approximately 1 mM) Tat was shown to exacerbate Parkinson-like locomotor deficit (Liu et al, 2014). This is consistent with reports showing methamphetamine-induced behavioral sensitization were enhanced in HIV-1 Tg rats (Kass et al, 2010). These data suggest Tat might directly or indirectly affect the cluster of dopamine neurons involved in regulation of locomotor activity.…”

Section: Dopaminergic Neurotransmission Hiv Infection and Tatsupporting

confidence: 93%

HIV, Tat and dopamine transmission

Gaskill

Miller

Gamble-George

et al. 2017

Neurobiology of Disease

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Human Immunodeficiency Virus (HIV) is a progressive infection that targets the immune system, affecting more than 37 million people around the world. While combinatorial antiretroviral therapy (cART) has lowered mortality rates and improved quality of life in infected individuals, the prevalence of HIV associated neurocognitive disorders is increasing and HIV associated cognitive decline remains prevalent. Recent research has suggested that HIV accessory proteins may be involved in this decline, and several studies have indicated that the HIV protein transactivator of transcription (Tat) can disrupt normal neuronal and glial function. Specifically, data indicate that Tat may directly impact dopaminergic neurotransmission, by modulating the function of the dopamine transporter and specifically damaging dopamine-rich regions of the CNS. HIV infection of the CNS has long been associated with dopaminergic dysfunction, but the mechanisms remain undefined. The specific effect(s) of Tat on dopaminergic neurotransmission may be, at least partially, a mechanism by which HIV infection directly or indirectly induces dopaminergic dysfunction. Therefore, precisely defining the specific effects of Tat on the dopaminergic system will help to elucidate the mechanisms by which HIV infection of the CNS induces neuropsychiatric, neurocognitive and neurological disorders that involve dopaminergic neurotransmission. Further, this will provide a discussion of the experiments needed to further these investigations, and may help to identify or develop new therapeutic approaches for the prevention or treatment of these disorders in HIV-infected individuals.

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Section: Dopaminergic Neurotransmission Hiv Infection and Tatsupporting

confidence: 93%

HIV, Tat and dopamine transmission

Gaskill

Miller

Gamble-George

et al. 2017

Neurobiology of Disease

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“…Deficits in learning, beginning at 5 months age, were observed in this model as well as neuroinflammation [28, 29]. This rat model has also been used successfully to reflect co-morbid effects of drugs of abuse on the CNS [30]. …”

Section: Rodent Models Of Hiv Diseasementioning

confidence: 99%

Rodent models for HIV-associated neurocognitive disorders

Gorantla

Poluektova

Gendelman

2012

Trends in Neurosciences

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Human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND) reflect the spectrum of neural impairments seen during chronic viral infection. Current research efforts focus on improving antiretroviral and adjunctive therapies, defining disease onset and progression, facilitating drug delivery, and halting neurodegeneration and viral resistance. As HIV is species-specific, generating disease in small animal models has proved challenging. After two decades of research, rodent HAND models now include those containing a human immune system. Antiviral responses, neuroinflammation and immunocyte blood-brain barrier (BBB) trafficking follow HIV infection in these rodent models. Here, we review these and other rodent models of HAND and discuss their unmet potential in reflecting human pathobiology and in facilitating disease monitoring and therapeutic discoveries.

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“…In a series of animal studies, stereotaxic microinjections of Tat and gp120 into the rat brain were accompanied by the exposure of animals to METH (Maragos et al 2002; Theodore et al 2006; Banerjee et al 2010), producing neurotoxicity. Using transgenic animal models of HIV-1 protein expression, METH has been demonstrated to have neurotoxic properties and alter behavioral endpoints (Kass et al 2010; Liu et al 2009; Silverstein et al 2011). Recent studies from our lab, suggest that METH can exacerbate behavioral deficits in HIV-1 transgenic animals (Moran et al 2012).…”

Section: Discussionmentioning

confidence: 99%

D1/NMDA Receptors and Concurrent Methamphetamine+HIV-1 Tat Neurotoxicity

Aksenov

Aksenova

Mactutus

et al. 2012

J Neuroimmune Pharmacol

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The interactive effects of HIV-1 infection and methamphetamine (METH) abuse in producing cognitive dysfunction represent a serious medical problem; however, the neural mechanisms underlying this interactive neurotoxicity remain elusive. In this study, we report that a combination of low, sub-toxic doses of METH + HIV-1 Tat 1–86 B, but not METH + HIV-1 gp120, directly induces death of rodent midbrain neurons in vitro. The effects of D1- and NMDA-receptor specific antagonists (SCH23390 and MK-801, respectively) on the neurotoxicity of different doses of METH or HIV-1 Tat alone and on the METH + HIV-1Tat interaction in midbrain neuronal cultures suggest that the induction of the cell death cascade by METH and Tat requires both dopaminergic (D1) and N-methyl D-aspartate (NMDA) receptor-mediated signaling. This interactive METH+Tat neurotoxicity does not occur in cultures of hippocampal neurons, which are predominately glutamatergic, express very low levels of dopamine receptors, and have no functional dopamine transporter (DAT). Thus, the presence of a subpopulation of neurons capable of dopamine release/uptake is essential for METH+Tat induction of the cell death cascade. Overall, our results support the hypothesis that METH and HIV-1 Tat disrupt the normal conjunction of signaling between D1 and NMDA receptors, resulting in neural dysfunction and death.

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Methamphetamine-Induced Behavioral and Physiological Effects in Adolescent and Adult HIV-1 Transgenic Rats

Cited by 26 publications

References 39 publications

HIV, Tat and dopamine transmission

HIV, Tat and dopamine transmission

Rodent models for HIV-associated neurocognitive disorders

D1/NMDA Receptors and Concurrent Methamphetamine+HIV-1 Tat Neurotoxicity

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