Abstract

Kindling, in the classical sense, involves progressively increasing responsivity to the intermittent repetition of the same 1-s subthreshold electrical stimulation over time, with the amygdala being the area most frequently studied. Such repeated subthreshold stimulation is associated with: lowering of the after-discharge (AD) threshold; lengthening and spread of the AD; marked seizure stage progression culminating in full-blown tonic-clonic forelimb convulsions with rearing and falling; and evolution from triggered to spontaneous seizures. This evolving process concomitantly involves changes in the spatio-temporal expression of immediate early genes (IEGs), neurotrophic factors, and late effector genes (LEGs), and an associated changing pattern of effectiveness of different pharmacological interventions. Since seizures are the paradigmatic behavioral manifestation of kindling, some types of pharmacological seizures, such as those induced by the local anesthetics cocaine and lidocaine, and some epileptic syndromes, are most likely homologously modeled by kindling. However, since non-epileptiform syndromes, such as recurrent episodes of affective illness and some pain syndromes possess non-homogenous elements of kindling-like evolution, some of the principles involved in kindling progression may, nonetheless, be pertinent to the understanding and treatment of these syndromes. For example, one could attempt to distinguish between the genes involved in the primary pathological processes of syndrome evolution versus those that are secondary and adaptive; such a differentiation could have important implications for the development of therapeutic approaches targeted to suppressing or enhancing these alterations, respectively. In these instances, inferences drawn from the kindling model are necessarily indirect and circumscribed because different neuroanatomical and biochemical processes are likely involved in the evolution of each neuropsychiatric syndrome. Given these recognized limitations of non-homologous models, kindling may still provide insights into the longitudinal course, progression, and treatment of some neuropsychiatric syndromes that can then be directly tested in the clinic.