Acute nicotine vapor normalizes sensorimotor gating and reduces locomotor activity deficits in HIV-1 transgenic rats

Jha, N. A.; Ayoub, S. M.; Flesher, M. M.; Morton, K.; Sikkink, M.; de Guglielmo, G.; Khokhar, J. Y.; Minassian, A.; Brody, A. L.; Young, J. W.

doi:10.1101/2024.06.18.599641

bioRxiv · 10.1101/2024.06.18.599641

Acute nicotine vapor normalizes sensorimotor gating and reduces locomotor activity deficits in HIV-1 transgenic rats

Jha, N. A.·Ayoub, S. M.·Flesher, M. M.·Morton, K.·Sikkink, M.·de Guglielmo, G.·Khokhar, J. Y.·Minassian, A.·Brody, A. L.·Young, J. W.

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Abstract

RationaleDespite improved life expectancy of people with HIV (PWH), HIV-associated neurocognitive impairment (NCI) persists, alongside deficits in sensorimotor gating and neuroinflammation. PWH exhibit high smoking rates, possibly due to neuroprotective, anti-inflammatory, and cognitive-enhancing effects of nicotine, suggesting potential self-medication. ObjectivesHere, we tested the effects of acute nicotine vapor exposure on translatable measures of sensorimotor gating and exploratory behavior in the HIV-1 transgenic (HIV-1Tg) rat model of HIV. MethodsMale and female HIV-1Tg and F344 control rats (n=57) were exposed to acute nicotine or vehicle vapor. Sensorimotor gating was assessed using prepulse inhibition (PPI) of the acoustic startle response, and exploratory behavior was evaluated using the behavioral pattern monitor (BPM). ResultsVehicle-treated HIV-1Tg rats exhibited PPI deficits at low prepulse intensities compared to F344 controls, as seen previously. No PPI deficits were observed in nicotine-treated HIV-1Tg rats, however. HIV-1Tg rats were hypoactive in the BPM relative to controls, whilst nicotine vapor increased activity and exploratory behavior across genotypes. Cotinine analyses confirmed comparable levels of the primary metabolite of nicotine across genotypes. ConclusionsPrevious findings of PPI deficits in HIV-1Tg rats were replicated and, importantly, attenuated by acute nicotine vapor. Evidence for similar cotinine levels suggest a nicotine-specific effect in HIV-1Tg rats. HIV-1Tg rats had reduced exploratory behavior compared to controls, attenuated by acute nicotine vapor. Therefore, acute nicotine may be beneficial for remediating sensorimotor and locomotor activity deficits in PWH. Future studies should determine the long-term effects of nicotine vapor on similar HIV/NCI-relevant behaviors.

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Jha, N. A., Ayoub, S. M., Flesher, M. M., Morton, K., Sikkink, M., de Guglielmo, G., Khokhar, J. Y., Minassian, A., Brody, A. L., Young, J. W.. 2024-06-22. Acute nicotine vapor normalizes sensorimotor gating and reduces locomotor activity deficits in HIV-1 transgenic rats. https://doi.org/10.1101/2024.06.18.599641

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