A chronic, low-dose treatment with methamphetamine modulates genes implicated in neurodegeneration in a transgenic model of NeuroHIV

Methamphetamine (METH) is a frequently abused addictive psychostimulant. METH use is highly prevalent in people living with HIV (PLWH). The HIV and drug interaction may promote progression of HAND, as PLWH who uses METH reportedly have increased neuronal injury, cognitive impairment and viral load. However, low concentration of METH has an approved clinical use as a treatment for patients diagnosed with attention-deficit/hyperactivity disorder (ADHD). Recent studies have also reported potential non-injurious effects via low-dose METH exposure, that improved learning and memory, and limited neuronal injury. This suggests that the specific dosage of METH plays a key role in determining whether the psychostimulant effects will be associated with apparent neurotoxicity or not. This study explored in vivo the effects of a long-term, low-dose METH regimen (12 weeks) in the HAND animal model with inducible expression of HIV-1 transactivator of transcription (Tat). In our observation, low dose of METH has a modulatory effect on learning and memory in the presence of the pathology-inducing HIV regulatory protein Tat. The observations from this study create the framework for future identification of potential targets for the treatment of neuroHIV/HAND in the context of psychostimulant use.