RETROVIRAL EFFECT ON BEHAVIORAL RESPONSE TO ABUSED DRUGS

描述：（申请人摘要）

DESCRIPTION: (Applicant's Abstract) Substance abuse and liability for HIV-1 infection are closely related. Many abused drugs impair immune function increasing the risk of infection per exposure as well as accelerating the proliferation of the retrovirus. Little is known regarding the effects of retroviral infection on the subjective response to drug administration. It is not clear whether HIV-1 infection increases. decreases or does not affect the user's perception of drug potency and efficacy. This laboratory has made extensive use of the LP-BM5 retroviral analog of AIDS in mice to study the cognitive and behavioral effects of retroviral infection. The murine AIDS (MAIDS) induced by LP-BM5 infection produces rapid and discrete impairment of learning and memory as well as alterations in CNS function. This impairment is produced well before the appearance of MAIDS-induced neurological deficits indicating that deficits result from impairment of acquisition or retrieval rather than motor performance. We have recently demonstrated that these mice can be trained to discriminate phencyclidine from saline in a nose poke. water reward system in a sensitive (Eve = 3mg/kg), robust (> 80% correct response) and specific manner. After in~ction with the LP-BM5 retrovirus, the potency of phencyclidine increases 10-fold with no effect on efficacy or specificity. We propose to determine whether infection of C57BI/6b mice with the LP-BM5 retrovirus alters the potency, efficacy, or specificity of interoceptive discrimination of pharmacological cues relevant to substance abuse. Thus, we will examine the effects of retroviral infection on the ability of mice to detect and respond to common drugs of abuse such as phencyclidines, ethanol, opioids and cocaine. In addition, we will examine the effects of LP-BM5 infection on the response to other drugs of abuse such as benzodiazepines and barbiturates. At monthly intervals, blood samples will be drawn for RT-PCR analysis of LP-BM5 titer. Repeated-measures ANOVA will be used for statistical analysis of pre-and post-infection drug sensitivity. In addition, regression analysis of drug behavioral effects as a function of RT-PCR-derived viral titer will determine the relationship between viral load and drug sensitivity. These studies will: l) provide basic information of the effects of retroviral infections such as LP-BM5 or HIV-l on the sensitivity of organisms to the subjective effects of drugs of abuse; 2) permit us to narrow the focus of future studies of the neurobiological effects of retroviral infection to sites which are behaviorally relevant and: 3) provide a specific focus for future collaborative studies of the effects of HIV- l infection on the subjective response to drugs of abuse in humans.