The mechanisms by which the recreational use of illicit drugs becomes compulsive have been the subject of a great deal of research. Much of this research has focused on ways in which addictive drugs usurp natural learning mechanisms, as well as the role for neuroadaptations in the dopamine (DA) system that may contribute to these effects. Recent reconceptualizations of the role of dopamine in learning have suggested that it may function as an error signal to cdrticolimbic target regions and that substances that interfere with normal dopamine functioning may pathologically-affect this signal. One of these disruptions may include interfering with a learning effect known as blocking, which limits the number of cues that can be associated with a given reward. This effect has been proposed to depend on the loss of phasic DA neuron discharge in response fully predicted rewards;because addictive drugs produce DA release due to their pharmacological effects, even after becoming fully predicted, they are theorized to negate the blocking effect.
The aim of this study is to examine this possibility. In the proposed study, the effect of methamphetamine (MA), cocaine (COC) and morphine (MO) on blocking will be examined using a conditioned place preference (CPP) and an instrumental learning procedure. These 3 substances will be contrasted due to the difference in the modes of action on DA release. In the first part of the study, rats will undergo CPP training with either MA, COC, MO, or vehicle (control) in a 3 chamber apparatus (1 neutral, 2 pairing chambers). Once the context-drug pairing is established, each of the pairing chambers will have a unique odor introduced and training will resume. Final testing will examine preference for the odor in a novel context. The instrumental portion of the study will examine the motivational properties of blocked versus unblocked cues in directing previously trained (i.e., nose poke) and novel (i.e., lever press) behaviors. I hypothesize that in the classical portion of the study rats will show no preference for the odor paired with food (as the odor will have been blocked by the context) but will show preference for odors paired with drug. In the instrumental portion, it is hypothesized that blocked cues will only direct behavior for subjects in one or more of the drug conditions but not for those in the food condition. Learning is used to guide behavior, and the blocking effect is one of the brain's tools for limiting the power of'a single reward. This study will assess a mechanism by which addictive drugs may be available to enter into a near infinite number of associations, creating for the chronic drug user a map of their surrounding marked with arrows leading towards their addictive substance of choice, leading to an insurmountable control over behavior by drugs and related cues.
