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Increases in compulsivity, inflammation, and neural injury in HIV transgenic rats with escalated methamphetamine self-administration under extended-access conditions.

Giordano de Guglielmo | Yu Fu | Jihuan Chen | Estefania Larrosa | Ivy Hoang | Tomoya Kawamura | Irene Lorrai | Barry Zorman | Joseph Bryant | Olivier George | Pavel Sumazin | Celine Lefebvre | Vez Repunte-Canonigo | Pietro Paolo Sanna
Brain research | 2020

The abuse of stimulants, such as methamphetamine (METH), is associated with treatment non-compliance, a greater risk of viral transmission, and the more rapid clinical progression of immunological and central nervous system human immunodeficiency virus (HIV) disease. The behavioral effects of METH in the setting of HIV remain largely uncharacterized. We used a state-of-the-art paradigm of the escalation of voluntary intravenous drug self-administration in HIV transgenic (Tg) and wildtype rats. The rats were first allowed to self-administer METH under short-access (ShA) conditions, which is characterized by a nondependent and more "recreational" pattern of METH use, and then allowed to self-administer METH under long-access (LgA) conditions, which leads to compulsive (dependent) METH intake. HIV Tg and wildtype rats self-administered equal amounts of METH under ShA conditions. HIV Tg rats self-administered METH under LgA conditions following a 4-week enforced abstinence period to model the intermittent pattern of stimulant abuse in humans. These HIV Tg rats developed greater motivation to self-administer METH and self-administered larger amounts of METH. Impairments in function of the medial prefrontal cortex (mPFC) contribute to compulsive drug and alcohol intake. Gene expression profiling of the mPFC in HIV Tg rats with a history of escalated METH self-administration under LgA conditions showed transcriptional evidence of increased inflammation, greater neural injury, and impaired aerobic glucose metabolism than wildtype rats that self-administered METH under LgA conditions. The detrimental effects of the interaction between neuroHIV and escalated METH intake on the mPFC are likely key factors in the greater vulnerability to excessive drug intake in the setting of HIV.

Pubmed ID: 31605699

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Associated grants

  • Agency: NIDA NIH HHS, United States
    Id: R01 DA048882
  • Agency: NIAID NIH HHS, United States
    Id: P30 AI036214
  • Agency: NIDA NIH HHS, United States
    Id: R01 DA043268
  • Agency: NIDA NIH HHS, United States
    Id: R01 DA041750
  • Agency: NIDA NIH HHS, United States
    Id: R01 DA046170
  • Agency: NIDA NIH HHS, United States
    Id: R01 DA046204

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