Nestler Lab

Laboratory of Molecular Psychiatry

Post Receptor Intracellular Signal Transduction Pathways

Drugs of abuse and stress affect the brain initially by influencing synaptic transmission:

  • drugs of abuse bind to synaptic targets
  • tress perturbs transmission at particular synapses in the brain

However, these acute actions of a drug or stress per se do not explain the long-term effects seen with repeated exposures. To understand such long-term effects, it is necessary to move beyond the classical view of a synapse to a more sophisticated, view, in which considers post-receptor, intracellular messenger pathways.

This means that, despite the initial actions of a drug or stress on the activity of a neurotransmitter or receptor system, the many actions of drugs and stress on brain function are achieved ultimately through the complex network of intracellular messenger pathways that mediate physiological responses to neurotransmitter-receptor interactions. These intracellular pathways consist of G proteins, second messenger systems, protein kinases, and protein phosphatases, among many others. Repeated exposure to drugs and stress would be expected to produce molecular and cellular adaptations as a result of repeated perturbation of these intracellular pathways. We believe that these adaptations are ultimately responsible for many features of addiction and depression.