Addiction and cognition

Abstract

The brain regions and neural processes that underlie addiction overlap extensively with those that support cognitive functions, including learning, memory, and reasoning. Drug activity in these regions and processes during early stages of abuse foster strong maladaptive associations between drug use and environmental stimuli that may underlie future cravings and drug-seeking behaviors. With continued drug use, cognitive deficits ensue that exacerbate the difficulty of establishing sustained abstinence. The developing brain is particularly susceptible to the effects of drugs of abuse; prenatal, childhood, and adolescent exposures produce long-lasting changes in cognition. Patients with mental illness are at high risk for substance abuse, and the adverse impact on cognition may be particularly deleterious in combination with cognitive problems related to their mental disorders.

FIGURE 1. A Cell Signaling Cascade in Learning and Memory

Glutamate binds to α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-d-aspartic acid (NMDA) receptors in the neuron membrane, opening channels for sodium and calcium to flow into the cell; calcium influx induces adenylate cyclase to convert adenosine triphosphate (ATP) to cyclic adenosine monophosphate (cAMP). cAMP triggers activation, sequentially, of protein kinase A (PKA), mitogen-activated protein kinase/extracellular signal-regulated protein kinase (MAPK/ERK), and cAMP response element-binding (CREB). CREB attaches to DNA, increasing DNA production of protein for the construction of new synapses. (For a detailed review of the cellular substrates of learning, see Abel and Lattal, 2001.)