Greater Sensitivity to the Stimulating and Anxiety-Like Effects of Methamphetamine in the HIV-1 Transgenic Rat
Year: 2009
Type: dissertation
Abstract: Methamphetamine (METH) abuse and the Human Immunodeficiency Virus (HIV) are highly comorbid illnesses, and over the past decade this comorbidity has come to be known as a double epidemic (Chang, Ernst, Speck, & Grob, 2005).METH can aggravate and promote the neuropathological deformations caused by HIV, resulting in severe cognitive and motor deficits.Among the HIV population, those who use METH have poorer prognosis and develop HIV-related pathologies sooner than nonusers (Cloak, Chang, Emst, Barr, Huitron-Resendiz, Sanchez-Alavez , et al., 2004).Highly active antiretroviral therapies (HAART) can slow the onset of profound neurological impairments such as HIV-associated dementia (HAD) and minor cognitive/motor disorders (MCMD).However, METH users will succumb to more severe cognitive and motor impairments, and at a faster rate, than nonusers despite the use of HAART.Because of this, new treatments will need to be developed to adequately treat the clinical profiles exhibited by METH users who are infected with the HIV virus.The study of METH use and HIV in an animal model may be of use to better develop treatment.Recently, a noninfectious HIV type 1 (HIV-1) transgenic (Tg) rat that displays many of the immune irregularities and clinical abnormalities seen in HIV patients was created (Reid, Sadowska, Denaro, Rao, Foullce, Hayes, et al., 2001).The HIV-1 Tg rat may be a useful animal model for evaluating the effects of METH in the presence of continuous HIV infection on brain function and behavior.The present set of experiments set out to establish an animal model of HIV-1 and METH use, and extrapolate findings to HIV-infected METH users.In Experiment One, Sprague-Dawley (SD) rats were used to develop a behavioral sensitization (BS) paradigm viii and examine drug context effects associated with BS of METH-induced behavior.Additionally, a modified context pre-exposure facilitation effect (CPFE) paradigm was implemented to assess the effects of METH on one-trial fear conditioning.Experiment Two utilized the HIV-1 Tg rat to evaluate the interactions between METH and the HIV-1 virus on BS, drug context effects, and the CPFE.The HIV-I Tg rat exhibited an augmented behavioral response to the psychoactivating properties of METH and increased sensitivity to a stressful event (i.e. a footshock).The maladaptive responses seen in the HIV-I Tg rat are likely mediated by neuroalterations associated with the virus.These studies indicate that the HIV-1 Tg rat may have a greater sensitivity to the stimulating and anxiety-like effects of METH.The differential effects of METH in HIV-1 Tg rats and normal controls have serious implications for the HIV-infected METH using population.
Author: Marley D. Kass
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W1517478009