Fragments of the stress hormone opiomelanocortin, administered peripherally, affect the kindling-induced electrical and behavioral phenomena in a complex way. The adrenocorticotrophe hormone (ACTH), derivatives ACTH 1-16, and melanocyte-stimulating hormone (MSH) related fragments (α- and ϒ2-MSH) seem to decrease synaptic efficacy as inferred from data on AD and BD durations. The opioid part of the molecule (ß-endorphin) or related opioid peptides may have opposite effects by increasing excitability and synaptic efficacy in the limbic system as showed by studies using the opioid antagonists naloxone and naltrexone. The classical stress hormone corticosterone of the adrenal cortex plays a role in synaptic plasticity as well. Although removal of the adrenal causes a temporary alteration, corticosterone administration reinstates brain excitability, and synaptic efficacy.
Social stressors of winning or losing a dyadic confrontation also affect plastic changes in brain function and behavior as induced by the kindling of the amygdala. Repeated winners, but not defeat experience, retards the development of AD, MS, and BD in kindled rats. Furthermore, the more offensive a winner rat is, the slower is the development of seizure behavior. This suggests that the study of coping with an environmental challenge that can be active or passive is of importance for plastic changes in the brain. Studies in rats selected for an aspect of coping style (e.g., active avoidance) suggests that genetic factors may be involved in the differential development of synaptic plasticity. That defeat, but not winner stress, reduces synaptic efficacy in rats with full-blown expression of kindling-induced seizure behavior suggests that both the brain state and the nature of stress, probably its controllability, is also of importance in synaptic plasticity. Finally, immunohistochemical data on muscarinergic acetylcholine receptor and the intracellular messenger protein kinase C distribution and qualities are presented that show that kindling has resulted in permanent changes in the cellular substrate of plasticity. Secondary foci are formed in limbic brain areas like the pyriform and entorhinal cortices that seem to affect the long-term existence of synaptic plasticity. The findings of all these experiments have been discussed in terms of stress, adaptation, and normal and pathological plasticities in the brain. In general, one may conclude that social stressors profoundly affect plastic changes of intercellular communication in the brain. Stress hormones like opiomelanocortins and corticosteroids may be the messengers of stressors.
These investigations were in part supported by the National Research Committee on Epilepsy of the Division for Health Research of the Netherlands Organization of Applied Science TNO (projects CLEO A65 and