Effects of Morphine on Behavioral Task Performance in SIV-Infected Rhesus Macaques

Abstract

The abuse of opiates such as morphine in synergy with HIV infection not only exacerbates neuropathogenesis but significantly impacts behavioral attributes in HIV infected subjects. Thus, the goal of the current study was to characterize behavioral perturbations in rhesus macaques subjected to chronic morphine and SIV infection. Specifically, we assessed three behavioral tasks: motor skill (MS), forelimb force (FFT) and progressive ratio (PR) tasks. After collecting baseline control data (44 weeks) and data during the morphine-only dependency period (26 weeks), a subset of animals were productively infected with neurovirulent strains of SIVmac (R71/E17) for an additional 33 weeks. A general pattern in the results is that behavioral decline occurred with high CSF viral loads but not necessarily with high plasma viral loads. Compared to saline controls, all treated animals showed significant decreases in performance on all three behavioral tasks during the morphine-only dependency period. During the post infection period, only the morphine plus SIV group showed a significant further decline and this only occurred for the MS task. Taken together, these data demonstrate a clear effect of morphine to produce behavioral deficits and also suggest that morphine can act synergistically with SIV/HIV to exacerbate behavioral deficits.

HIV Tat and Morphine-induced Neurodegeneration in a Beclin 1 Hemizygous Mouse Model

“…Interestingly, there seemed to be an interactive effect, though independent of strain, in Tat and morphine treated mice on day 5. This has also been shown in studies on the effects of morphine on behavioral task performance in SIV-infected rhesus macaques [432].…”

Opioid and neuroHIV Comorbidity – Current and Future Perspectives

“…• Morphine, DAMGO (ex vivo) ↓ [ 35 S]GTPγS binding in NAc Shell, CPu, amygdala, PFC, but not hippocampus, with morphine in Tat mice Mouse, Tat tg, males (Hahn et al 2016 ) Neuroinflammation; morphine tolerance (antinociception), physical withdrawal, reward Tat 1–86 No Morphine (75 mg pellet, 5 days) • ↑ Tolerance (↓ anti-nociceptive potency and ↓ withdrawal symptoms) • ↑ CPP and cytokines (24 h after withdrawal) • Above effects reduced by CCR5 blockade Mouse, Tat tg, males (Gonek et al 2018 ) Neuropathy gp120 (0.2 μg), q.d. intrathecally No Morphine (3 μg, intrathecally, b.i.d., 5 days) • ↑ Mechanic allodynia • ↑ Brd4 mRNA Rat, males, gp120 (Takahashi et al 2018 ) Morphine efficacy, potency Tat 1–86 No Morphine (acute, 2–8 mg/kg s.c.) ↓ Antinociceptive potency and efficacy (tail flick) Mouse, Tat tg, males (Fitting et al 2012 ) Morphine tolerance, physical dependence Tat 1–86 No Morphine (75 mg pellet, 4 days) • ↑ Antinociceptive tolerance • ↓ Physical dependence Mouse, Tat tg, males (Fitting et al 2016 ) Locomotor function Tat 1–86 No Oxycodone (0–10 mg/kg, i.p., 15 min prior behavioral assay) ↑ Locomotor activity, center entries (open field) Mouse, Tat tg, females (Salahuddin et al 2020 ) SIV macR71/17E No Morphine (escalating doses of 1–2.5 mg/kg i.m., q.i.d., 59 weeks) ↓ Motor skill Rhesus macaques (Marcario et al 2016 ) Tat 1–86 No Oxycodone (acute, 0.1–10 mg/kg, i.p.) ↑ Psychomotor effects Mouse, Tat tg, females (Paris et al 2020 ) BBB integrity Tat ...…”

Morphine Suppresses Peripheral Responses and Transforms Brain Myeloid Gene Expression to Favor Neuropathogenesis in SIV Infection

“…NHP infection by SIV remains the best model for the study of HIV pathogenesis and treatment, including neuropathogenesis (32)(33)(34)(35)(36)(37). NHPs are also an excellent animal model for studying the effects of drugs of abuse and their interactions with SIV infection, especially for effects on the brain (38)(39)(40)(41)(42). Such animal experiments allow better controlled conditions than observational studies in humans.…”