Methamphetamine and Amphetamine Differentially Affect Associative Learning: Behavioral and Neurobiological Correlates by Darien

One factor hypothesized to contribute significantly to addiction processes is maladaptive associative learning wherein substance-related cues become closely associated with the drug response. These strong associations are thought to contribute significantly to drug craving and promote the cycle of abuse by increasing susceptibility to relapse. One goal of the studies presented here was to model aspects of the addiction process by examining psychostimulant-induced alterations of associative learning, and how specific neurobiological mechanisms, namely glucocorticoid or dopamine receptor activation, contribute to these alterations. A second goal was to investigate potential differences in the effects of two psychostimulants; methamphetamine (METH) and amphetamine (AMPH). These drugs were chosen because, while structurally very similar, they have differing abuse liabilities. Some of the disparities in rates of use and abuse can be accounted for by availability, with METH being more affordable and easier to obtain than AMPH. However, increasing diversion of prescription AMPH for nonmedical use is thought to contribute to the rise in prescription drug abuse indicating that it is unlikely to be just a question of greater availability of METH. There are many methods by which the effects of psychostimulants on associative learning can be assessed, however two particular techniques, Pavlovian-to-instrumental transfer (PIT) and sensitization, were chosen for use in the studies presented here. In Experiment 1, a sensitization paradigm was utilized to determine whether repeated administration of low to moderate doses of AMPH or METH result in differing levels of locomotor sensitization, conditioned locomotor behavior, or cross-sensitization. The results of this study suggest that both drugs elicit approximately equal levels of