clear because both serotonergic and adrenergic medications are helpful. Dopaminergic medications have little antidepressant efficacy, however, although dopamine seems so critical for hedonic tone or at least euphoria. Direct evidence for neurobiological connections between drug dependence and psychiatric disorders remains to be elucidated and may be studied with newly developed tools (e.g., functional brain imaging).

HIV Models

The utility of an animal model rests in its ability to permit the study of a disease process under controlled conditions. Animal models that recapitulate the pathogenic and functional outcomes seen with HIV infection in humans can then be used to examine the influence of drugs of abuse on HIV disease progression. Direct neurotoxic effects of drugs, in addition to their effects on immunocompetence, may contribute to an enhancement of neurological sequelae of AIDS (called neuroAIDS disease) or accelerate its onset. These studies also will help determine the nature of viral neuropathogenesis to specific brain systems relevant to drug reward. That may have significant clinical outcomes related to risk reduction in terms of altered behavioral and pharmacological sensitivity to drugs of abuse in infected individuals. Thus, behavioral analysis in animal models of viral neuropathogenesis provides a unique opportunity to study the interaction between drugs of abuse and the immune system and should go far in identifying critical viral- and host-derived factors associated with increased susceptibility to the pathobiological effects of drugs of abuse and consequent synergistic neurotoxicity. Continued development of animal models of the effects of HIV infection on the brain would be useful for studying the links between AIDS and drug abuse—e.g., effects of drugs on disease progression, and the effect of HIV on brain reward systems and behaviors relevant to risk.

Neurotoxicity of Drug Dependence

There were early reports that chronic exposure to drugs of abuse led to neuronal death. Most reports proved to be spurious, however this is still a controversial area. One example of drug-induced neurotoxicity remains well established, namely the ability of certain amphetamine derivatives to kill central monoaminergic neurons. Methamphetamine and to a lesser extent amphetamine are toxic to midbrain dopamine neurons (Seiden et al., 1975), and methylenedioxymethamphetamine (MDMA, also known as Ecstasy) is toxic to midbrain serotonin neurons (Ricaurte et al., 1988).

More recently, subtler forms of neural injury have been detected in



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