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HIV-1 Tat and morphine decrease murine inter-male social interactions and associated oxytocin levels in the
Sara R Nass1, Arianna R S Lark1, Yun K Hahn2
1Department of Pharmacology and Toxicology, Virginia Commonwealth University, Medical College of Virginia (MCV) Campus, Richmond, VA 23298-0613, USA.
Abstract:
Many persons infected with HIV-1 (PWH) and opioid-dependent individuals experience deficits in sociability that interfere with daily living. Sociability is regulated by the prefrontal cortico-hippocampal-amygdalar circuit. Within this circuit HIV-1 trans-activator of transcription (HIV-1 Tat) and opioids can increase dendritic pathology and alter neuronal firing. Changes in sociability are also associated with dysregulation of hypothalamic neuropeptides such as oxytocin or corticotropin releasing factor (CRF) in the prefrontal cortico-hippocampal-amygdalar circuit. Accordingly, we hypothesized that the interaction of HIV-1 Tat and morphine would impair inter-male social interactions and disrupt oxytocin and CRF within the PFC and associated circuitry. Male mice were exposed to HIV-1 Tat for 8 weeks and administered saline or escalating doses of morphine twice daily (s.c.) during the last 2 weeks of HIV-1 Tat exposure. Tat attenuated aggressive interactions with an unknown intruder, whereas morphine decreased both non-aggressive and aggressive social interactions in the resident-intruder test. However, there was no effect of Tat or morphine on non-reciprocal interactions in the social interaction and novelty tests. Tat, but not morphine, decreased oxytocin levels in the PFC and amygdala, whereas both Tat and morphine decreased the percentage of oxytocin-immunoreactive neurons in the hypothalamic paraventricular nucleus (PVN). In Tat(+) or morphine-exposed mice, regional levels of CRF and oxytocin correlated with alterations in behavior in the social interaction and novelty tests. Overall, decreased expression of oxytocin in the prefrontal cortico-hippocampal-amygdalar circuit is associated with morphine- and HIV-Tat-induced deficits in social behavior.
Insights
HIV-1 Tat and morphine impair social behavior by disrupting oxytocin levels in brain circuits. This research highlights neurobiological links between HIV-1 infection, opioid use, and social deficits.
Area of Science:
- Neuroscience
- Immunology
- Pharmacology
Background:
- Individuals with HIV-1 infection and opioid dependence often exhibit social interaction deficits.
- Sociability is regulated by the prefrontal cortico-hippocampal-amygdalar circuit, which is affected by HIV-1 trans-activator of transcription (Tat) and opioids.
- Dysregulation of hypothalamic neuropeptides, including oxytocin and corticotropin-releasing factor (CRF), is linked to social behavior changes.
Purpose of the Study:
- To investigate the combined effects of HIV-1 Tat and morphine on social interactions in male mice.
- To examine the impact of HIV-1 Tat and morphine on oxytocin and CRF levels within the prefrontal cortex (PFC) and associated brain circuitry.
- To determine the correlation between neuropeptide levels and behavioral alterations.
Main Methods:
- Male mice were exposed to HIV-1 Tat for 8 weeks.
- Morphine or saline was administered during the final 2 weeks of Tat exposure.
- Social interactions were assessed using the resident-intruder test, social interaction test, and novelty test.
- Oxytocin and CRF levels, as well as oxytocin-immunoreactive neurons, were measured in specific brain regions (PFC, amygdala, hypothalamic paraventricular nucleus).
Main Results:
- HIV-1 Tat exposure alone attenuated aggressive social interactions.
- Morphine administration decreased both aggressive and non-aggressive social interactions.
- Tat, but not morphine, reduced oxytocin levels in the PFC and amygdala.
- Both Tat and morphine decreased the percentage of oxytocin-immunoreactive neurons in the hypothalamic paraventricular nucleus (PVN).
- Regional CRF and oxytocin levels correlated with behavioral changes in social interaction and novelty tests.
Conclusions:
- Decreased oxytocin expression in the prefrontal cortico-hippocampal-amygdalar circuit is associated with social behavior deficits induced by morphine and HIV-1 Tat.
- These findings elucidate the neurobiological mechanisms underlying social impairments in HIV-1 infected and opioid-dependent individuals.
- Targeting oxytocin pathways may offer therapeutic potential for social deficits in these populations.
