HIV gp120 impairs nucleus accumbens neuroimmune function and dopamine D3 receptor-mediated inhibition of cocaine seeking in male rats

Namba, Mark D.; Phillips, Megan N; Chen, Peng‐Jen; Blass, Benjamin E.; Neisewander, Janet L.

doi:10.1016/j.addicn.2023.100062

Cited by 3 publications

(4 citation statements)

References 107 publications

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“…Future studies should combine results from various modalities to better understand the impact of drug-induced changes in dopaminergic systems involved in HIV. Dopamine dysregulation may underlie the drug hypersensitization and cognitive deficits observed in rodent models of HAND with meth or cocaine exposure [17,19,20,79,80,105,108,119,120,132,133,181]. There is limited characterization of the cognitive deficits associated with HIV+/CUD+ and HIV+/MUD+.…”

Section: Discussionmentioning

confidence: 99%

“…While HIV+/CUD+ and HIV+/MUD+ have similar complex relationships between their biological, behavioral, and social mechanisms, the mechanisms investigated have differed. Pre-clinical and clinical studies on the combined effects of HIV and cocaine exposure have focused on impairments in reward function, decision-making, and altered structure and function in dopaminergic brain regions [17,19,20,80,94,108,138,139,143]. On the other hand, pre-clinical and clinical evidence on the combined effects of HIV and meth exposure have focused on molecular-based effects, such as dysregulation in the expression of cellular signaling proteins and mitochondrial dysfunction [18,105,106,131,134,177].…”

Section: Discussionmentioning

confidence: 99%

“…Abstinence from chronic cocaine self-administration and gp120 protein expression decreases responsiveness to pharmacological interventions. MC-25-41, a weak D3R partial agonist, has been shown to reduce cocaine motivation in rats; however, in a study that administered MC-25-41 to rats with and without gp120 expression, reduced cue-induced cocaine seeking occurred only in rats without gp120 expression [80]. This evidence suggests that HAND may reduce treatment efficacy for cocaine seeking, highlighting the importance of investigating novel therapeutic interventions for people living with HAND and CUD.…”

Section: Gp120/cocainementioning

confidence: 98%

“…Tat and gp120 expression in transgenic rodents have been used to study the combined effects of HIV-1 and psychostimulant drug exposure. Expressing these viral proteins in transgenic rodents can help elucidate mechanisms behind the altered dopaminergic systems observed in these comorbid conditions [78][79][80]. However, since these models only express some HIV-1 viral proteins, results from these models may miss the interactive and additive effects among these proteins.…”

Section: Neuropathological Alterations In Hiv and Evidence For Dopami...mentioning

confidence: 99%

See 3 more Smart Citations

Neurological, Behavioral, and Pathophysiological Characterization of the Co-Occurrence of Substance Use and HIV: A Narrative Review

Vines,

Sotelo,

Giddens

et al. 2023

Brain Sciences

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Combined antiretroviral therapy (cART) has greatly reduced the severity of HIV-associated neurocognitive disorders in people living with HIV (PLWH); however, PLWH are more likely than the general population to use drugs and suffer from substance use disorders (SUDs) and to exhibit risky behaviors that promote HIV transmission and other infections. Dopamine-boosting psychostimulants such as cocaine and methamphetamine are some of the most widely used substances among PLWH. Chronic use of these substances disrupts brain function, structure, and cognition. PLWH with SUD have poor health outcomes driven by complex interactions between biological, neurocognitive, and social factors. Here we review the effects of comorbid HIV and psychostimulant use disorders by discussing the distinct and common effects of HIV and chronic cocaine and methamphetamine use on behavioral and neurological impairments using evidence from rodent models of HIV-associated neurocognitive impairments (Tat or gp120 protein expression) and clinical studies. We also provide a biopsychosocial perspective by discussing behavioral impairment in differentially impacted social groups and proposing interventions at both patient and population levels.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Gp120/cocainementioning

confidence: 98%

Section: Neuropathological Alterations In Hiv and Evidence For Dopami...mentioning

confidence: 99%

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Neurological, Behavioral, and Pathophysiological Characterization of the Co-Occurrence of Substance Use and HIV: A Narrative Review

Vines,

Sotelo,

Giddens

et al. 2023

Brain Sciences

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Advancing the preclinical study of comorbid neuroHIV and substance use disorders: Current perspectives and future directions

Namba

Xie

Barker

2023

Brain, Behavior, and Immunity

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EcoHIV Infection Modulates the Effects of Cocaine Exposure Pattern and Abstinence on Cocaine Seeking and Neuroimmune Protein Expression in Male Mice

Namba,

Xie,

Park

et al. 2024

Preprint

Self Cite

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Cocaine use disorders (CUDs) and human immunodeficiency virus (HIV) remain persistent public health dilemmas throughout the world. One major hurdle for treating CUD is the increase in cocaine craving and seeking behavior that occurs over a protracted period of abstinence, an effect known as the incubation of craving. Little is known about how HIV may modulate this process. Thus, we sought to examine the impact of chronic HIV infection on the incubation of cocaine craving and associated changes in the central and peripheral immune systems. Here, mice were inoculated with EcoHIV, which is a chimeric HIV-1 construct that produces chronic HIV infection in mice. EcoHIV- and sham-infected mice were conditioned with cocaine daily or intermittently in a conditioned place preference (CPP) paradigm, followed by 1 or 21 days of forced abstinence prior to assessing preference for the cocaine-paired chamber. Under both conditioning regimens, sham mice exhibited incubation of cocaine CPP after 21 days of abstinence. EcoHIV-infected mice conditioned daily with cocaine showed enhanced cocaine seeking at both abstinence timepoints, whereas infected mice conditioned intermittently showed a reversal of the incubation effect, with higher cocaine seeking after 1 day of abstinence compared to 21 days. Analysis of corticolimbic CX3CL1-CX3CR1 and glutamate receptor expression revealed alterations in medial prefrontal cortex (mPFC) CX3CL1 and nucleus accumbens (NAc) GluN2A receptors that correlated with cocaine seeking following daily cocaine exposure. Moreover, examination of peripheral immune markers showed that the effect of abstinence and EcoHIV infection on these measures depended on the cocaine exposure regimen. Altogether, these results highlight the importance of cocaine abstinence and exposure pattern as critical variables that modulate HIV-associated neuroimmune outcomes and relapse vulnerability.

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HIV gp120 impairs nucleus accumbens neuroimmune function and dopamine D3 receptor-mediated inhibition of cocaine seeking in male rats

Cited by 3 publications

References 107 publications

Neurological, Behavioral, and Pathophysiological Characterization of the Co-Occurrence of Substance Use and HIV: A Narrative Review

Neurological, Behavioral, and Pathophysiological Characterization of the Co-Occurrence of Substance Use and HIV: A Narrative Review

Advancing the preclinical study of comorbid neuroHIV and substance use disorders: Current perspectives and future directions

EcoHIV Infection Modulates the Effects of Cocaine Exposure Pattern and Abstinence on Cocaine Seeking and Neuroimmune Protein Expression in Male Mice

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