HIV-1 Tat and morphine decrease murine inter-male social interactions and associated oxytocin levels in the prefrontal cortex, amygdala, and hypothalamic paraventricular nucleus

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 op...

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Published in:Hormones and behavior 2021-07, Vol.133, p.105008-105008, Article 105008
Main Authors: Nass, Sara R., Lark, Arianna R.S., Hahn, Yun K., McLane, Virginia D., Ihrig, Therese M., Contois, Liangru, Napier, T. Celeste, Knapp, Pamela E., Hauser, Kurt F.
Format: Article
Language:English
Subjects:
Aggression
Corticotropin releasing factor
Endogenous opioid system
Hippocampus
HIV-associated neurocognitive disorders
Opiate abuse
Paraventricular nucleus of the hypothalamus
Resident-intruder
Social anxiety
Social interaction
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Summary: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. •HIV-1 Tat reduces aggressive inter-male interactions in the resident-intruder test.•Morphine decreases inter-male social interactions in the resident-intruder test.•HIV-1 Tat decreases oxytocin levels in the PFC and amygdala, but not hippocampus.•Oxytocin and CRF levels correlate with behavior in Tat(+) or morphine exposed mice.•Morphine and Tat decrease the percentage of oxytocin cells in the hypothalamic PVN.
ISSN:0018-506X
1095-6867
DOI:10.1016/j.yhbeh.2021.105008