Methamphetamine-Induced Behavioral Sensitization Is Enhanced in the HIV-1 Transgenic Rat
- 253 Downloads
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.
Keywordsmethamphetamine behavior HIV dopaminergic prefrontal cortex
This study was supported, in part, by National Institutes of Health (NIH) grants K02-DA016149 and R21-DA019836 (SLC) and K24-DA016170 (LC).
- Bjorklund NL, Sorg BA, Schenk JO (2008) Neuronal dopamine transporter activity, density and methamphetamine inhibition are differentially altered in the nucleus accumbens and striatum with no changes in glycosylation in rats behaviorally sensitized to methamphetamine. Synapse 62:736–745. doi: 10.1002/syn.20528 PubMedCrossRefGoogle Scholar
- Cho AK, Melega WP, Kuczenski R, Segal DS (2001) Relevance of pharmacokinetic parameters in animal models of methamphetamine abuse. Synapse 39:161–166. doi: 10.1002/1098-2396(200102)39:2<161::AID-SYN7>3.0.CO;2-E PubMedCrossRefGoogle Scholar
- Ferris MJ, Mactutus CF, Booze RM (2008) Neurotoxic profiles of HIV, psychostimulant drugs of abuse, and their concerted effect on the brain: current status of dopamine system vulnerability in NeuroAIDS. Neurosci Biobehav Rev 32:883–909. doi: 10.1016/j.neubiorev.2008.01.004 PubMedCrossRefGoogle Scholar
- Hamamura T, Akiyama K, Akimoto K, Kashihara K, Okumura K, Ujike H, Otsuki S (1991) Co-administration of either a selective D1 or D2 dopamine antagonist with methamphetamine prevents methamphetamine-induced behavioral sensitization and neurochemical change, studied by in vivo intracerebral dialysis. Brain Res 546:40–46. doi: 10.1016/0006-8993(91)91156-U PubMedCrossRefGoogle Scholar
- Reid W, Sadowska M, Denaro F, Rao S, Foulke J Jr, Hayes N, Jones O, Doodnauth D, Davis H, Sill A, O’Driscoll P, Huso D, Fouts T, Lewis G, Hill M, Kamin-Lewis R, Wei C, Ray P, Gallo RC, Reitz M, Bryant J (2001) An HIV-1 transgenic rat that develops HIV-related pathology and immunologic dysfunction. Proc Natl Acad Sci USA 98:9271–9276. doi: 10.1073/pnas.161290298 PubMedCrossRefGoogle Scholar
- Rhodes SD, Hergenrather KC, Yee LJ, Knipper E, Wilkin AM, Omli MR (2007) Characteristics of a sample of men who have sex with men, recruited from gay bars and Internet chat rooms, who report methamphetamine use. AIDS Patient Care STDS 21:575–583. doi: 10.1089/apc.2007.0002 PubMedCrossRefGoogle Scholar
- Seiden LS, Ricaurte GA (1987) Neurotoxicity of methamphetamine and related drugs. In: Meltzer HY (ed) Psychopharmacology: the third generation of progress. Raven, New York, pp 359–366Google Scholar
- Shuto T, Seeman P, Kuroiwa M, Nishi A (2008) Repeated administration of a dopamine D1 receptor agonist reverses the increased proportions of striatal dopamine D1High and D2High receptors in methamphetamine-sensitized rats. Eur J NeuroSci 27:2551–2557. doi: 10.1111/j.1460-9568.2008.06221.x PubMedCrossRefGoogle Scholar