Methamphetamine-induced behavioral sensitization is enhanced in the HIV-1 transgenic rat

J Neuroimmune Pharmacol. 2009 Sep;4(3):309-16. doi: 10.1007/s11481-009-9160-8. Epub 2009 May 15.

Abstract

Methamphetamine (METH) addiction is prevalent among individuals with HIV infection. We hypothesize that HIV-positive individuals are more prone to METH use and to the development of METH dependence. To test this hypothesis, we examined the effects of METH (daily intraperitoneal injection 2.5 mg/kg for 6 days) on rearing and head movement in 12-13-week-old male HIV-1 transgenic (HIV-1Tg) rats compared to F344 control rats as an indicator of behavioral sensitization, also representing neural adaptation underlying drug dependence and addiction. Body and brain weights were also recorded. The involvement of the dopaminergic system was investigated by examining dopamine receptors 1 (D1R) and 2 (D2R) and dopamine transporter (DAT) expression in the striatum and prefrontal cortex. METH increased rearing number and duration in both F344 and HIV-1Tg rats. Rearing number was attenuated over time, whereas rearing duration remained constant. METH also induced a progressive increase in stereotypical head movement in both F344 and HIV-1Tg rats, but it was greater in the HIV-1Tg rats than in the F344 animals. The brain to body weight ratio was significantly lower in METH-treated HIV-1Tg rats compared to F344 controls. There was no significant difference in striatal D1R, D2R, or DAT messenger RNA in HIV-1Tg and F344 rats. However, D1R expression was greater in the prefrontal cortex of HIV-1Tg rats than F344 rats and was attenuated by METH. Our results indicate that METH-induced behavioral sensitization is greater in the presence of HIV infection and suggest that D1R expression in the prefrontal cortex may play a role in METH addiction in HIV-positive individuals.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amphetamine-Related Disorders / genetics*
  • Amphetamine-Related Disorders / psychology
  • Animals
  • Animals, Genetically Modified
  • Anti-HIV Agents / therapeutic use
  • Behavior, Animal / drug effects*
  • Body Weight / drug effects
  • Brain / pathology
  • Central Nervous System Stimulants / pharmacology*
  • Dopamine Plasma Membrane Transport Proteins / genetics
  • Fusion Proteins, gag-pol / genetics
  • HIV Infections / genetics
  • HIV Infections / psychology*
  • HIV-1 / genetics*
  • Head Movements / drug effects
  • Male
  • Methamphetamine / pharmacology*
  • Neostriatum / drug effects
  • Neostriatum / metabolism
  • Organ Size / drug effects
  • Prefrontal Cortex / drug effects
  • Prefrontal Cortex / metabolism
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Rats
  • Rats, Inbred F344
  • Receptors, Dopamine D1 / drug effects
  • Receptors, Dopamine D1 / genetics
  • Receptors, Dopamine D2 / drug effects
  • Receptors, Dopamine D2 / genetics
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Anti-HIV Agents
  • Central Nervous System Stimulants
  • Dopamine Plasma Membrane Transport Proteins
  • Fusion Proteins, gag-pol
  • RNA, Messenger
  • Receptors, Dopamine D1
  • Receptors, Dopamine D2
  • Methamphetamine