Both HIV Infection and Conditional Tat Expression Decrease Prepulse Inhibition with Further Impairment by Methamphetamine History in Humans

Walter, T.; Young, J.; Milienne-Petiot, M.; Deben, D. S.; Heaton, R.; Letendre, S.; Grelotti, D.; Perry, W.; Grant, I.; Minassian, A.

doi:10.1101/2020.06.11.130666

bioRxiv · 10.1101/2020.06.11.130666

Both HIV Infection and Conditional Tat Expression Decrease Prepulse Inhibition with Further Impairment by Methamphetamine History in Humans

Walter, T.·Young, J.·Milienne-Petiot, M.·Deben, D. S.·Heaton, R.·Letendre, S.·Grelotti, D.·Perry, W.·Grant, I.·Minassian, A.

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Abstract

HIV infection and methamphetamine (METH) use are highly comorbid and represent a significant public health problem. Both conditions are known to negatively impact a variety of brain functions. One brain function that may be affected by HIV and METH use is sensorimotor gating, an automatic, pre-conscious filtering of sensory information that is thought to contribute to higher order cognitive processes. Sensorimotor gating is often measured using prepulse inhibition (PPI), a paradigm that can be conducted in both humans and animals, thereby enabling cross-species translational studies. While previous studies suggest HIV and METH may individually impair PPI, little research has been conducted on the effects of combined HIV and METH on PPI. The goal of this cross-species study was to determine the effects of METH on PPI in the inducible Tat (iTat) mouse model of HIV and in people with HIV. PPI was measured in the iTat mouse model before, during, and after chronic METH treatment and after Tat induction. Chronic METH treatment decreased PPI in male but not female mice. PPI normalized with cessation of METH. Inducing Tat expression decreased PPI in male but not in female mice. No interactions between chronic METH treatment and Tat expression were observed in mice. In humans, HIV was associated with decreased PPI in both men and women. Furthermore, PPI was lowest in people with HIV who also had a history of METH dependence. Overall, these results suggest HIV and METH may additively impair early information processing in humans, potentially affecting downstream cognitive function. HIGHLIGHTSO_LIHIV decreased PPI in men and women C_LIO_LIPPI was most decreased in people with HIV and a history of METH dependence C_LIO_LIChronic METH treatment decreased PPI in male but not female mice C_LIO_LITat expression decreased PPI in male but not female mice C_LIO_LIChronic METH treatment and Tat expression did not interact to affect PPI in mice C_LI

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Walter, T., Young, J., Milienne-Petiot, M., Deben, D. S., Heaton, R., Letendre, S., Grelotti, D., Perry, W., Grant, I., Minassian, A.. 2020-06-12. Both HIV Infection and Conditional Tat Expression Decrease Prepulse Inhibition with Further Impairment by Methamphetamine History in Humans. https://doi.org/10.1101/2020.06.11.130666

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