Role of dopamine in memory consolidation

Dopamine (3,4-dihydroxyphenethylamine, DA) is a neuroendocrine transmitter belonging to the catecholamine and phenethylamine families. DA in the brain plays a critical role in modulating a variety of actions on neuroendocrine and behavioral systems. Pathological change in DA transmission is a key feature of many neurological and psychiatric disorders, such as schizophrenia, Parkinson's disease, Tourette's syndrome, and many others. Theories on the behavioral function of DA in the brain have advanced from the original proposal that DA could mediate the hedonic impact of rewards and motor behavior, to the hypothesis that this system may mediate incentive salience to reward-related stimuli. More recently it has been proposed that DA mediates reinforcement learning. Even if the theoretical debate around DA function continues, the central role of this neurotransmitter as a mediator of memory formation is being widely recognized. Memory has been distinguished, according to a temporal gradient, as: short-term memory, which lasts from seconds to minutes, and long term memory, which lasts from hours to years. The two forms of memory rely on different neural substrates and are affected by different pharmacological manipulations. Long-term memory has been further distinguished into different categories depending on the kind of learning mechanism activated. The multiple memory system theory, in fact, posits that long-term memory can be distinguished into explicit and implicit memories. Explicit memory derives from relational and/or action-outcome learning mechanisms that lead to the formation of mental representation of events, contexts, or instrumental actions. Explicit memory is thought to be dependent upon the activity of regions located in the cortico-limbic systems (i.e., hippocampus). Implicit memory is formed through stimulus-response learning and leads to the incremental acquisition of skills and habits, and it is dependent on the activity of sensorimotor systems (i.e., the dorsal striatum). DA modulates the activity of both of these neuronal pathways, and therefore it mediates the formation of different forms of memory. In this chapter we will first describe the characteristics and general functions of the dopaminergic system, including an overview of the pharmacological agents available to modulate it. Then we will discuss the involvement of DA in learning and memory within this theoretical framework. In particular, we will review pre-clinical behavioral pharmacological experiments using DAergic drugs to manipulate DA activity, supporting the role for DA in modulating different forms of memory during the consolidation phase.