Methamphetamine-Induced Behavioral Sensitization Is Enhanced in the HIV-1 Transgenic Rat

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.

NeuroHIV and Use of Addictive Substances

“…They found that METH induced an increase in body temperature, rearing, and stereotypical head movement over days (behavioral sensitization) in both the HIV-1Tg and F344 rats, but with greater changes occurring in HIV-1Tg rats. METH attenuated the expression of the DA receptor, D1R, in the PFC of the HIV-1Tg rats, but not in the F344 rats (Liu et al, 2009). In another study, HIV-1Tg rats were shown to be more prone to both the behavioral sensitization and acute physiological effects (hyperthermia) of METH than the control rats (Kass, Liu, Vigorito, Chang, & Chang, 2010).…”

“…In summary, the presence of HIV-1 viral proteins leads to a decrease in DA receptors (Liu et al, 2009) and may explain the behavioral evidence that indicates that HIV-1Tg rats are more prone to addiction (Chang & Connaghan, 2012;.…”

“…The HIV-1 proteins, Tat and gp120, are toxic to DA neurons (Gurwell et al, 2001;Nath et al, 2000), and HIV-1 impacts DA neurons in subcortical structures, particularly those in the basal ganglia (Urbina & Jones, 2004). Both HIV-1 patients (Wang et al, 2004) and HIV-1Tg rats (Liu et al, 2009) have been reported to have fewer DA receptors. Volkow et al (2001) found that individuals with fewer DA receptors are at a higher risk for substance abuse due to their increased sensitivity to the pleasurable effects of those substances.…”

“…Although METH is considered more potent than cocaine and other drugs of abuse in increasing synaptic levels of DA (Di Chiara & Imperato, 1988), only a few studies have investigated how HIV infection affects the use of METH. Liu et al (2009) compared the physiological and behavioral parameters as well as DA receptor and DAT expression in the STR and PFC of young adult male HIV-1Tg rats with those of F344 control animals following daily injections of METH for 6 days. They found that METH induced an increase in body temperature, rearing, and stereotypical head movement over days (behavioral sensitization) in both the HIV-1Tg and F344 rats, but with greater changes occurring in HIV-1Tg rats.…”

Intra-ventral tegmental area HIV-1 Tat1–86 attenuates nicotine-mediated locomotor sensitization and alters mesocorticolimbic ERK and CREB signaling in rats

“…Tat transgenic mice exhibit increased DA transporter expression (Perry et al, 2010). HIV-1 transgenic rats show enhanced behavioral sensitization to methamphetamine (Liu et al, 2009; Kass et al, 2010) but attenuated nicotine-mediated behavioral sensitization (Midde et al, 2011). These studies suggest that HIV-1 viral proteins alter dopaminergic pathways that in part, mediate behavioral sensitization.…”