Neuropeptides and electroconvulsive treatment

Neuropeptides: corticotropin releasing factor (CRF), neuropeptide Y (NPY) a nd somatostatin (STS) have been associated with depression and anxiety, whi le neurotensin (NT), calcitonin gene-related peptide (CGRP) and tachykinins [neurokinin A (NKA) and substance P (SP)] are presumed to also play a role in the function of the dopaminergic system. Moreover, investigations in th e past decade have shown that psychotomimetics and antipsychotic drugs as w ell as lithium affect brain synthesis, tissue concentrations, and release o f some neuropeptides. In view of the above, experiments were carried out to explore whether changes in neuropeptides constitute one of the mechanisms of action of electroconvulsive treatment (ECT). Human cerebrospinal fluid ( CSF) was studied before and after ECT, and brains from healthy and models o f depression rats were investigated in electroconvulsive stimuli (ECS)-trea ted and sham-treated animals. The major findings were that a series of ECTs , in parallel to clinical recovery, increased CSF concentrations of NPY-lik e immunoreactivity (-LI), STS-LI, and CRF-LI, and in one study endothelin-L I. A series of ECS, but not a single treatment, reproducibly elevated conce ntrations of NPY-LI, NKA-LT, and STS-LI-but not NT-LI, SP-LI, galanin-ll, o r CGRP-LI-in hippocampus, frontal cortex, and occipital cortex. No changes were measured in other regions, e.g., striatum. NPY and STS mRNAs were also increased indicating that ECS affects peptide synthesis. Generalized seizu res induced by, e.g., kainic acid or pentylenetetrazole, had similar effect s on neuropeptides. The changes persisted for at least 1 week after the Las t treatment. Pretreatment with compounds reducing seizures, such as benzodi azepines and MK-801, had no effect on magnitude of neuropeptide changes alt hough the seizure duration was decreased by >50%. On the basis of these fin dings, it is suggested that neuropeptides are involved in ECT's mechanisms of action. Since ECT is therapeutically efficient in both schizophrenia and depression and, taking into account that antipsychotic drugs and psychotom imetics as well as lithium selectively affect some neuropeptides, it is hyp othesized that distinct combinations of neuropeptide and monoamine changes in selected neuronal populations constitute the underpinnings of ECT's effe cts on specific disease symptoms, conceivably independent of diagnosis.