UC San Diego

Stimulants are prescribed widely to treat a number of disorders, including narcolepsy, shift work sleep disorder, and attention deficit hyperactivity disorder. These prescription stimulants are also commonly, illicitly used for studying and general cognitive enhancement, a trend referred to today as academic doping. Higher doses of stimulants may also be self-administered with a rapid route of administration (e.g., smoking, intravenous injection), leading instead to cognitive impairments and addiction. Few studies have examined the parameters outlining when stimulants switch from being nootropic to harmful. This dissertation proposes that, along with route of administration, dose is the critical component dictating the cognitive effects of stimulants. Chapter 1 describes our first study examining the dose-dependent effects of stimulants on fear conditioning, using cocaine. The lowest dose of cocaine enhanced learning, while the highest dose impaired it. Chapter 2 follows with a description of the dose-dependent effects of amphetamine on fear conditioning. Similarly, the lowest doses of amphetamine enhanced learning, while the highest doses led to impairment. Chapter 3 outlines our attempts to extrapolate the amphetamine results to a related form of learning, extinction. We utilized low dose amphetamine to increase extinction learning, but found that no dose facilitated extinction, compared to placebo. Chapter 4 looks further into the structure of fear conditioning, examining the relationships between the most commonly reported training and testing measures. Our analyses demonstrate that post-shock freezing is highly correlated with context fear, confirming that the post-shock measure is better described as a context measure rather than a conditioned response. Our analyses also indicate that tone baseline freezing is not independent from tone test freezing, confounding the most common ways of reporting tone fear. Chapter 5 concludes the dissertation with a broad overview of popular stimulants today, their mechanisms of action, and effects on cognition. A continuum of activation is proposed, in which low doses of stimulants lead to increased concentration and cognitive performance, while high doses lead to cognitive impairments and addiction