Dataset Information

HIV transgenic rats demonstrate impaired sensorimotor gating, but are insensitive to cannabinoid (Δ9-tetrahydrocannabinol)-induced deficits.

ABSTRACT:

Background

HIV-associated Neurocognitive Disorder (HAND) is commonly observed in persons living with HIV (PWH), and is characterized by cognitive deficits implicating disruptions of fronto-striatal neurocircuitry. Such circuitry is also susceptible to alteration by cannabis and other drugs of abuse. PWH use cannabis at much higher rates than the general population, thus prioritizing the characterization of any interactions between HIV and cannabinoids on cognitively relevant systems. Prepulse inhibition (PPI) of the startle response, the process by which the motor response to a startling stimulus is attenuated by perception of a preceding non-startling stimulus, is an operational assay of fronto-striatal circuit integrity that is translatable across species. PPI is reduced in PWH. The HIV transgenic (HIVtg) rat model of HIV infection mimics numerous aspects of HAND, although to date the PPI deficit observed in PWH has yet to be fully recreated in these animals.

Methods

PPI was measured in male and female HIVtg rats and wildtype (WT) controls following acute, nonconcurrent treatment with the primary constituents of cannabis-Δ 9-tetrahydrocannabinol (THC; 1 & 3 mg/kg, s.c) and cannabidiol (CBD; 1, 10, & 30 mg/kg, i.p.).

Results

HIVtg rats exhibited a significant PPI deficit relative to WT controls. THC reduced PPI in controls, but not HIVtg rats. CBD exerted only minor, genotype-independent effects on PPI.

Conclusions

HIVtg rats exhibit a relative insensitivity to the deleterious effects of THC on the fronto-striatal function reflected by PPI, which may partially explain the higher rates of cannabis use amongst PWH.

SUBMITTER: Roberts BZ

PROVIDER: S-EPMC8598295 | biostudies-literature |

REPOSITORIES: biostudies-literature

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