Molecular psychiatry. Adaptations of receptor-coupled signal transduction pathways underlying stress- and drug-induced neural plasticity.

Abstract

Advances in molecular biology and neuroscience are leading to new opportunities for elucidation of the pathophysiology of psychiatric disorders and the long-term actions of psychotropic drugs. The actions of first messengers, including neurotransmitters, neuropeptides, and neurotrophins, on neuronal function can now be viewed in terms of their regulation of complex intracellular signal transduction pathways. These pathways mediate most actions of first messengers, including fast mediatory (e.g., cell firing), short-term modulatory (e.g., neuronal metabolism, receptor sensitivity, neurotransmitter sensitivity), and long-term modulatory (e.g., gene expression). Moreover, it is becoming increasingly evident that adaptations of receptor-coupled intracellular pathways, referred to here as neural plasticity, mediate the long-term actions of psychotropic drug treatments. In addition, an inability to mount the appropriate adaptive responses to environmental stressors could contribute to the pathophysiology of psychiatric disorders. The following provides a brief overview of receptor-coupled intracellular signal transduction pathways in brain and general mechanisms of neural plasticity. Specific examples of neural plasticity in response to stress, antidepressant treatments, and drugs of abuse are discussed in greater detail. Continued elucidation of the intracellular signal transduction pathways which govern neuronal function and the mechanisms that mediate neural plasticity will provide the basis for the development of more effective and fast-acting therapeutic agents, as well as identification of the abnormalities underlying psychiatric disorders.