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Effects of Morphine on Behavioral Task Performance in SIV-Infected Rhesus Macaques
Joanne K Marcario1, Gurudutt Pendyala2, Mariam Riazi1
1Department of Molecular & Integrative Physiology, University of Kansas Medical Center, 3901 Rainbow Blvd., mailstop 3043, Kansas City, KS, 66160-7336, USA.
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.
Insights
Chronic morphine use and SIV infection worsen behavioral deficits in macaques. Morphine alone caused declines, and combined with SIV, led to further motor skill impairment, especially with high CSF viral loads.
Area of Science:
- Neuroscience
- Behavioral Science
- Infectious Disease Research
Background:
- Opiate abuse, particularly morphine, exacerbates neuropathogenesis and impacts behavior in HIV-infected individuals.
- Understanding the combined effects of morphine and SIV/HIV is crucial for managing neurological and behavioral comorbidities.
Purpose of the Study:
- To characterize behavioral changes in rhesus macaques under chronic morphine administration and SIV infection.
- To investigate the synergistic effects of morphine and SIV on motor skills, forelimb force, and motivation.
Main Methods:
- Rhesus macaques underwent baseline behavioral assessments (motor skill, forelimb force, progressive ratio tasks).
- Animals received chronic morphine or saline, followed by infection with neurovirulent SIVmac strains in a subset.
- Behavioral performance was monitored throughout baseline, morphine-dependency, and post-infection periods.
Main Results:
- Morphine administration alone significantly decreased performance across all tested behavioral tasks compared to controls.
- Infection with SIV led to further significant declines in motor skills for the morphine-plus-SIV group.
- Behavioral decline correlated with high cerebrospinal fluid (CSF) viral loads, not necessarily plasma viral loads.
Conclusions:
- Morphine significantly induces behavioral deficits.
- Morphine acts synergistically with SIV/HIV infection to exacerbate behavioral impairments.
- CSF viral load is a key indicator of morphine and SIV-induced behavioral dysfunction.
