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Long term administration of methamphetamine in Tat mice causes altered behavior and neuroplasticity gene expression – Implications in neuroAIDS
Author(s) -
Nookala Anantha Ram,
Kumar Anil
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.705.8
Subject(s) - methamphetamine , neuroplasticity , elevated plus maze , neurotoxicity , open field , medicine , pharmacology , endocrinology , anxiety , toxicity , psychiatry
Methamphetamine (MA) abuse is common among individuals infected with HIV‐1 and is shown to affect the disease progression towards AIDS. These HIV‐1 infected individual's exhibit greater neuronal injury and higher cognitive decline. Several HIV‐1 proteins, specifically gp120 and HIV‐1 Tat have been shown to affect neurocognition. HIV‐1 Tat, a viral protein released early during HIV‐1 replication has been implicated in HIV‐associated neurotoxicity mediated through production of pro‐inflammatory cytokines, reactive oxygen species and dysregulation of neuroplasticity among many other factors in the central nervous system. However, combined effect of methamphetamine and HIV‐1 Tat on the alteration of locomotor function, anxiety, memory and their correlation to neuroplasticity gene expression is not well documented. The present study was undertaken to determine the combined effect of methamphetamine and HIV‐1 Tat on behavior and neuroplasticity gene expression. Doxycycline (DOX)‐inducible HIV‐1 Tat (1–86) transgenic mice were administered 6mg/kg MA twice a day. Expression of Tat in various brain regions was confirmed by RT‐PCR. Behavior studies were performed in both males and female mice after 2 weeks of MA administration. As measured by open field assay, the ambulatory activity was decreased in Tat mice. However, administration of MA increased the ambulatory activity in both Tat −ve mice and Tat +ve mice. MA administered mice have showed decreased anxiety levels as assessed by the time spent in the light compartment during Light/dark box assay. In water maze task, there was a significant increase in escape latency in all the groups compared to control mice, particularly more in Tat transgenic mice that were administered MA. We looked at the alterations in behavior with correlation to neuroplasticity gene expression. We observed a significant decrease in the protein expression of CNTF, Lif in entorhinal cortex and prefrontal cortex. Furthermore, we observed decrease in mRNA expression of CNTF, IL‐11 and BDNF in parietal cortex. This study therefore provides novel insights into the interaction of HIV‐1 Tat and MA on the dysregulated expression of various neuroplasticity genes in different brain regions. Support or Funding Information The work was supported by National Institute on Drug Abuse grants DA025528 & DA025011.