The Clinical and Molecular Neurobiology of Substance Use Disorders: Focus on Marijuana, Cocaine, and Methamphetamine

Substance use disorders are biopsychosocial problems that have substantial negative impact on the lives of individuals and their family members. These disorders are defined as compulsive abuse of licit or illicit substances despite adverse medicolegal consequences. Research is being conducted to characterize the neuropsychiatric and cognitive manifestations of some of these disorders with the goal of developing treatments that might improve deficits associated with the use of these drugs. Investigators are also investigating the molecular neurobiological and neuropathological bases of these disorders.  The hope is to develop an overarching neurobiological understanding that might be translatable to beneficial pharmacological therapies. In my talk I will discuss some of the cognitive deficits that include decision making and memory functions that have been reported in chronic marijuana and cocaine users. I will also report on the use of the rat model to mimic methamphetamine addiction. These rats are taught to self-administer methamphetamine. Because these self-administration (SA) models do not include adverse consequences that are necessary to reach a diagnosis of addiction in humans by the DSM, we trained rats to self-administer methamphetamine for 20 days and then we punished lever-presses for methamphetamine with mild footshocks of increasing intensity for 5 days. Response-contingent punishment significantly reduced methamphetamine taking in some rats (shock-sensitive, SS) but not in others (shock-resistant, SR).  I will discuss results showing significant changes in epigenetic markers in the nucleus accumbens of the addicted and non-addicted rats. We can therefore conclude that adverse consequences can differentiate addicted from non-addicted rats and that there are substantial differences in the brain of these animals. Dissection of the impact of these epigenetic differences may help to plan better pharmacological treatments for substance use disorders.

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