Drugs of Abuse, Dopamine, and HIV-Associated Neurocognitive Disorders/HIV-Associated Dementia

Purohit, Vishnudutt; Rapaka, Rao S.; Shurtleff, David B.

doi:10.1007/s12035-011-8195-z

Cited by 111 publications

(108 citation statements)

References 74 publications

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“…Substance abuse is highly comorbid with HIV infection (Mathers et al, 2008;Purohit et al, 2011), but relatively little is known regarding how HIV may impact the rewarding effects of abused drugs. These experiments utilized a bigenic mouse model capable of brain-specific expression of HIV-Tat protein to examine the hypothesis that exposure to Tat protein was sufficient to influence the psychostimulant and rewarding effects of cocaine.…”

Section: Discussionmentioning

confidence: 99%

“…Importantly, these studies revealed extinction on a magnitude commensurate with non-Tat-induced controls, suggesting that some effects for drug reward may not be pervasive, and a therapeutic window for treatments targeting central Tat proteins (Mousseau et al, 2012) may prove efficacious. Given that psychostimulant users comprise a significant segment of the population of HIV-infected patients (UNAIDS/WHO, 2005; Mathers et al, 2008), and HIV-infected drug users present with a more marked neurological progression of HIV dementia (UNAIDS/WHO, 2005;Purohit et al, 2011), studies examining the synergy between drug abuse and neurotoxic substances released during HIV infection such as Tat (Aksenov et al, 2001; may offer new insights into the behavioral changes correlated with the progression of HIV-1 Tat infection.…”

Section: Discussionmentioning

confidence: 99%

“…HIV-infected, drug-abusing individuals may experience more severe or faster-progressing HIV-1 related neurological impairment (UNAIDS/WHO, 2005). Dopaminergic systems otherwise known to mediate drug reward (Di Chiara et al, 2004;Kalivas and Volkow, 2005;Purohit et al, 2011) may be modified by chronic cocaine use (such as the up-or downregulation of cocaine recognition sites on dopamine (DA) transporters; Malison et al, 1998;Staley et al, 1994;Wilson et al, 1996), and are also implicated in the pathogenesis of HIV-1-associated neurological complications (Berger and Arendt, 2000;Cass et al, 2003). Consistent with this, autopsy of HIV-1 infected brains demonstrates infiltration of HIV-infected cells in DA-rich regions (Navia et al, 1986), and such patients often present comorbid clinical signs common to dopaminergic disorders (Nath, 1999).…”

Section: Introductionmentioning

confidence: 99%

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Effects of Conditional Central Expression of HIV-1 Tat Protein to Potentiate Cocaine-Mediated Psychostimulation and Reward Among Male Mice

Paris

Carey

Shay

et al. 2013

Neuropsychopharmacol

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As a major neuropathogenic factor associated with human immunodeficiency virus (HIV) infection, HIV-1 Tat protein is known to synergize with psychostimulant drugs of abuse to cause neurotoxicity and exacerbate the progression of central nervous system pathology. However, the functional consequences of the interaction between HIV-1 Tat and abused drugs on behavior are little known. We tested the hypothesis that HIV-1 Tat expression in brain would modulate the psychostimulant effects of cocaine. Using the GT-tg bigenic mouse model, where brain-selective Tat expression is induced by activation of a doxycycline (Dox) promotor, we tested the effects of Tat on cocaine (10 mg/kg, s.c.) induced locomotion and conditioned place preference (CPP). Compared with uninduced littermates or C57BL/6J controls, cocaine-induced hyperlocomotion was sustained for a significantly longer duration among Tat-induced mice. Moreover, although all groups displayed similar saline-CPP, Tat-induced GT-tg mice demonstrated a three-fold increase in cocaine-CPP over the response of either uninduced littermates or Dox-treated C57BL/6J control mice. Induction of Tat also increased the magnitude of a previously established cocaine-CPP after an additional cycle of cocaine place-conditioning. Despite Tat-induced potentiation, extinction of place preference occurred within 21 days, commensurate with cocaine-extinction among saline-treated littermates and C57BL/6J controls. Re-exposure to cocaine produced reinstatement of an equivalent place preference in Tat-induced GT-tg or C57BL/6J mice; however, induction of Tat protein after the extinction of CPP also produced reinstatement without additional exposure to cocaine. Together, these data suggest that central HIV-1 Tat expression can potentiate the psychostimulant behavioral effects of cocaine in mice.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Effects of Conditional Central Expression of HIV-1 Tat Protein to Potentiate Cocaine-Mediated Psychostimulation and Reward Among Male Mice

Paris

Carey

Shay

et al. 2013

Neuropsychopharmacol

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“…We have observed a "flattening" of the ISI function in rats administered apomorphine (Moran et al, 2009), comparable to the ISI functions exhibited by the HIV-1 Tg rats in the present study. Although other neural systems may be involved, central DA system dysfunction often results from HIV-1 infection and is associated with subsequent cognitive deficits (Kumar et al 2011;diRocco et al 2000;Chang et al 2008;Wang et al 2004; for review, see Purohit et al 2011). The use of behavioral measures such as the ASR and PPI that can detect early neurological alterations, especially those of the DA system, may be instrumental in predicting the development of HAND and thus determining an appropriate course of treatment.…”

Section: Discussionmentioning

confidence: 99%

Time and time again: Temporal processing demands implicate perceptual and gating deficits in the HIV-1 transgenic rat

Moran¹,

Booze²,

Mactutus³

2014

Neurotoxicology and Teratology

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“…Accumulating evidence indicates that HIV-encoded proteins, such as gp120, contribute to neuronal dysfunction in the basal ganglia (Purohit et al, 2011). Moreover, the presence of gp120 in the brain may increase the susceptibility to methamphetamine-induced neurotoxicity and exacerbate neuronal dysfunction in HIV+ individuals.…”

Section: Introductionmentioning

confidence: 99%

Methamphetamine Exposure Combined with HIV-1 Disease or gp120 Expression: Comparison of Learning and Executive Functions in Humans and Mice

Kesby

Heaton

Young

et al. 2015

Neuropsychopharmacol

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Methamphetamine dependence is a common comorbid condition among people living with HIV, and may exacerbate HIV-associated neurocognitive disorders. Animal models of neuroAIDS suggest that the gp120 protein may also cause cognitive impairment. The present work evaluated the separate and combined effects of HIV/gp120 and methamphetamine on learning and executive functions in both humans and transgenic mice. Human participants were grouped by HIV serostatus (HIV+ or HIV − ) and lifetime methamphetamine dependence (METH+ or METH − ). A neurocognitive test battery included domain-specific assessments of learning and executive functions. Mice (gp120+ and gp120 − ) were exposed to either a methamphetamine binge (METH+) or saline (METH − ), then tested in the attentional-set-shifting task to assess learning and executive functions. In humans, HIV status was associated with significant impairments in learning, but less so for executive functions. The frequency of learning impairments varied between groups, with the greatest impairment observed in the HIV+/METH+ group. In mice, gp120 expression was associated with impairments in learning but not reversal learning (executive component). The greatest proportion of mice that failed to complete the task was observed in the gp120 +/METH+ group, suggesting greater learning impairments. Our cross-species study demonstrated that HIV in humans and gp120 in mice impaired learning, and that a history of methamphetamine exposure increased the susceptibility to HIV-associated neurocognitive deficits in both species. Finally, the similar pattern of results in both species suggest that the gp120 protein may contribute to HIV-associated learning deficits in humans.

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Drugs of Abuse, Dopamine, and HIV-Associated Neurocognitive Disorders/HIV-Associated Dementia

Cited by 111 publications

References 74 publications

Effects of Conditional Central Expression of HIV-1 Tat Protein to Potentiate Cocaine-Mediated Psychostimulation and Reward Among Male Mice

Effects of Conditional Central Expression of HIV-1 Tat Protein to Potentiate Cocaine-Mediated Psychostimulation and Reward Among Male Mice

Time and time again: Temporal processing demands implicate perceptual and gating deficits in the HIV-1 transgenic rat

Methamphetamine Exposure Combined with HIV-1 Disease or gp120 Expression: Comparison of Learning and Executive Functions in Humans and Mice

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