Common Molecular and Cellular Substrates of Addiction and Memory

Drugs of abuse cause long-lasting changes in the brain that underlie the behavioral abnormalities associated with drug addiction. Similarly, experience can induce memory formation by causing stable changes in the brain. Over the past decade, the molecular and cellular pathways of drug addiction, on the one hand, and of learning and memory, on the other, have converged. Learning and memory and drug addiction are modulated by the same neurotrophic factors, share certain intracellular signaling cascades, and depend on activation of the transcription factor CREB. They are associated with similar adaptations in neuronal morphology, and both are accompanied by alterations in synaptic plasticity (e.g., long-term potentiation, long-term depression) at particular glutamatergic synapses in the brain. There has also been recent convergence in the brain regions now considered important sites for molecular and cellular plasticity underlying addiction and memory. Complex circuits involving the hippocampus, cerebral cortex, ventral and dorsal striatum, and amygdala are implicated both in addiction and in learning and memory. The complexity of the plasticity that occurs in these circuits can be illustrated by CREB, which induces very different behavioral effects in these various brain regions. A better understanding of the molecular and cellular adaptations that occur in these neural circuits may lead to novel interventions to improve memory and combat addiction in humans.