Developmental Brain Research, 37 (1987) 43-58 43 Elsevier BRD 50633 The susceptibility of rats to pilocarpine-induced seizures is age-dependent Esper A. Cavalheiro l, Delrio F. Silva l, Waldemar A. Turski 2, Lineu S. Caldera Filho 1, Z u n e r A. B o r t o l o t t o I and L e c h os law Turski 2'* I Laboratorio de Neurologia Experimental, Departamento de Neurologia e Neurocirurgia, Escola Paulista de Medici (Brazil) and 2Department of Pharmacology, Medical School, Lublin (Poland) (Accepted 28 April 1987) Key words: Pilocarpine; Maturation; Seizure; Brain damage; Development; Rat Behavioral, electroencephalographic and morphological changes induced by systemic administration of pilocarpine hydro were studied in 3-90-day-old rats. Pilocarpine, 100, 200 and 380 mg/kg, presented a characteristic array of behavioral pat veloping rats. Hyper- or hypoactivity, tremor, loss of postural control, scratching, head bobbing and myoctonic movemen limbs dominated the behavior in 3-9-day-old rats. No overt motor seizures were observed in this age group. More intense b signs evolving in some animals to limbic seizures and status epilepticus occurred when pilocarpine was administered in 12 The electrographic activity in these animals progressed from low voltage spiking registered concurrently in the hippocamp tex during the first week of life into localized epileptic activity in the hippocampus, which spread to cortical recordings dur ond week of life. No morphological alterations were detected in the brains of 3-12-day-old rats subjected to the action of pi 100-380 mg/kg. The adult pattern of behavioral and electroencephalographic sequelae after pilocarpine was encountered day-old rats. Akinesia, tremor and head bobbing progressed in 15-21-day-old rats given pilocarpine, 100-380 mg/kg, to mot seizures and status epilepticus. The lethal toxicity of pilocarpine reached 50% during the third week of life. This increased ty to the convulsant action of pilocarpine was characterized by a shortened latency for behavioral and electrographic signs creased severity of seizures relative to older and younger rats. In 15-21-day-old rats subjected to pilocarpine-induced co high voltage fast activity superposed over hippocampal 0-rhythm, progressed into high voltage spiking and spread to cortic The electrographic activity became well synchronized and then developed into seizures and status epilepticus. Morpholog of frontal forebrain sections in 15-21-day-old rats which underwent status epilepticus after pilocarpine revealed no damage tenuated pattern of damage. In 15-21-day-old rats which presented epilepsy-related brain damage, morphological break seen in the hippocampus, amygdala, olfactory cortex, neocortex and certain thalamic nuclei. No damage was detected in th tia nigra and lateral thalamic nucleus. An adult pattern of the damage to the brain, in terms of extent and topography, was 4-5-week-old rats. The increased susceptibility to the convulsant action of pilocarpine observed during the third week of lif decreased with age and reached the mature level in 35-60-day-old rats. The different sensitivity of developing rats to the co action of pilocarpine may be related to the immaturity of neuronal networks in the brain engaged in the generation and spr zure activity. INTRODUCTION 'Psychomotor' or temporal lobe epilepsy is the most c o m m o n form of epilepsy in adult m a n 19'3°'44. This form of epilepsy is seen in children only after the age of 3 years 19. The clinical experience has until re- cently left some uncertainty as to whether spread of seizures, and extent and topographyof the seizure- related cell deathin i m m a t u r e h u m a n brain resem- bles that c o m m o n l y seen in adults suffering from complex partial seizures 19.30. The pilocarpine model of epilepsy offers an attrac- tive feature in that intractable seizures a n d status epi- lepticus can be induced rapidly following pilocarpine treatment. In addition, s p o n t a n e o u s m o t or seizures continue to be observed several weeks after treat- * Present address: Department of Neuropsychopharmacology, Schering AG, P.O. Box 650133, Sellerstr. 6-8, D-1000 F.R.G. Correspondence: E.A. Cavalheiro, Laboratorio de Neurologia Experimental, Departamento de Neurologia e Neurocirurgia, Es Paulista de Medicina, R. Botucatu 862, CEP 04023 Sao Paulo, SP, Brazil. 0165-3806/87/$03.50 © 1987 Elsevier Science Publishers B.V. (Biomedical Division)