Suppression of amygdala kindling with short interstimulus intervals: effect of norepinephrine depletion

The rate of development of generalized kindled convulsions was profoundly influenced by the interval between amygdala stimulations. With stimulation every 10 min, nearly complete interference with the progression of kindling was observed in most rats, and hourly stimulation precipitated kindling rates three times longer than did once per day. Depletion of norepinephrine (NE), as a result of intracerebroventricular pretreatment with 6-hydroxydopamine, virtually eliminated the interference with kindling development seen in the vehicle control rats. Such depletion of NE, however, had little influence on the generalized responses once developed. At this stage, interference with seizure provocation was observed as truncated electroencephalographic seizures which were usually devoid of motor correlates. This interference was more profound in the shorter interstimulus intervals and was independent of NE depletion. Finally, when changing from the short kindling intervals of 10 min and 1 h to the longer interval of 24 h, an unexpected interference with seizure provocation was observed. The implication of these results for the biochemical basis of kindling and kindling as a model of learning are discussed.