Alteration in pattern of EEG activities and convulsant effect of cocaine following chronic adminsitration in the rhesus monkey.

The effects of chronic administration of high doses of cocaine were studied in monkeys (Ss) with electrodes implanted in the brain. The Ss were injected daily with cocaine at a minimal convulsant dose (MCD) during polygraphic recording of EEGs, eye movement, respiratory and heart rates. The initial cocaine MCDs ranged from 3.2 to 6.5 mg/kg i.v. in ten Ss and markedly increased on each successive day following repeated daily injection (75--100% increase within 5--12 days). The elevated daily cocaine MCD was maintained for 1.5--2 months, and thereafter it gradually decreased and stabilized at levels between 20 and 30% above baseline within 2 months. During this period, the duration of daily convulsions evoked by cocaine MCD markedly decreased and stabilized at a constant level (30--35 sec) along with the latency of convulsions. The pattern of daily convulsions evoked by cocaine MCD changed from multiple episodes of intermittent tonic-clonic convulsions, which occurred during the earlier stage (1--2 months) of chronic treatment, to a single episode of sustained tonic-clonic convulsion. The Ss became extremely placid and tame or were profoundly depressed in their overall behavior most of the time. Simultaneously, the Ss continuously showed persistent rhythmic slow waves (5--6 c/sec) predominantly in the neocortex and limbic system structures. The results strongly suggested that chronic cocaine administration at high doses caused relatively permanent alteration of EEGs and behavior in the Ss, and the limbic system structures played an important role in the effect.