Inhibitory Control Deficits Associated with Upregulation of CB 1 R in the HIV-1 Tat Transgenic Mouse Model of Hand

AbstractIn the era of combined antiretroviral therapy, HIV-1 infected individuals are living longer lives; however, longevity is met with an increasing number of HIV-1 associated neurocognitive disorders (HAND) diagnoses. The transactivator of transcription (Tat) is known to mediate the neurotoxic effects in HAND by acting directly on neurons and also indirectly via its actions on glia. The Go/No-Go (GNG) task was used to examine HAND in the Tat transgenic mouse model. The GNG task involves subjects discriminating between two stimuli sets in order to determine whether or not to inhibit a previously trained response. Data reveal inhibitory control deficits in female Tat(+) mice (p = .048) and an upregulation of cannabinoid type 1 receptors (CB1R) in the infralimbic (IL) cortex in the same female Tat(+) group (p <  .05). A significant negative correlation was noted between inhibitory control and IL CB1R expression (r = −.543,p = .045), with CB1R expression predicting 30% of the variance of inhibitory control (R2 = .295,p = .045). Furthermore, there was a significant increase in spontaneous excitatory postsynaptic current (sEPSC) frequencies in Tat(+) compared to Tat(−) mice (p = .008, across sexes). The increase in sEPSC frequency was significantly attenuated by bath application of PF3845, a fatty acid amide hydrolase (FAAH) enzyme inhibitor (p <  .001). Overall, the GNG task is a viable measure to assess inhibitory control deficits in ...
Source: Journal of NeuroImmune Pharmacology - Category: Drugs & Pharmacology Source Type: research