Inhibitory Control Deficits Associated with Upregulation of CB1R in the HIV-1 Tat Transgenic Mouse Model of Hand
Year: 2019
Type: article
Abstract: In 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 (CB 1 R) in the infralimbic (IL) cortex in the same female Tat(+) group ( p < .05). A significant negative correlation was noted between inhibitory control and IL CB 1 R expression ( r = −.543, p = .045), with CB 1 R expression predicting 30% of the variance of inhibitory control ( R 2 = .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 Tat transgenic mice and results suggest a potential therapeutic treatment for the observed deficits with drugs which modulate endocannabinoid enzyme activity. Results of the Go/No-Go operant conditioning task reveal inhibitory control deficits in female transgenic Tat(+) mice without significantly affecting males. The demonstrated inhibitory control deficits appear to be associated with an upregulation of cannabinoid type 1 receptors (CB 1 R) in the infralimbic (IL) cortex in the same female Tat(+) group.
Institutions: University of North Carolina at Chapel Hill, North Carolina Central University, Medical University of South Carolina, Scripps Research Institute, Indiana University Bloomington, Indiana University, Virginia Commonwealth University, Okinawa Institute of Science and Technology Graduate University
Language: English
Subfield: Pharmacology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,760
Awards: G120164892, G1279806978, Mapping HIV-Tat +/- endocannabinoid induced synaptic changes at the macromolecular level via cryo-electron tomography, G170969906, G239716963, G2443072965, G2673341756, G3059896207, G3593534703, G41423929, G4248876272, G4932312460, Endocannabinoid-mediated neuroprotection in models of neuroAIDS in vivo, G6355676074, Tuning the master clock of the brain: Endocannabinoid modulation of the olivo-cerebellar system and animal behavior, G8868675294, G959726013
OpenAlex ID: W2965310939