Motor and emotional disturbances developing in rats receiving daily subthreshold injections of picrotoxin

Abstract

MOTOR AND EMOTIONAL DISTURBANCES DEVELOPING IN RATS RECEIVING DAILY SUBTHRESHOLD INJECTIONS OF PICROTOXIN Go N. Kryzhanovskii,* A. A. Shandra, UDC 616.8-009.1+616.89-008.48]- R. Fo Makul'kin, L. S. Godlevskii~ 092.9-02:615.214.31 and A~ M. Mazarati KEY WORDS: picrotoxin kindling; seizure syndrome; akinetic syndrome; defensive be- havior syndrome~ pathological system~ pathological determinant Chronic administration of metrazol in a subconvulsive dose causes the development of pre- disposition to seizures, manifested as an increase in the intensity of responses to metrazol, ranging from individual twitches to generalized clonicotonic convulsions [3, 8, i0]. The phe- nomenon also is characterized by lowering of the seizure threshold relative to metrazol for a long period of time after its administration has ceased, i.e., it has the basic features of kindling and is defined as pharmacologic kindling [3, 8]. Besides the seizure changes, dur- ing kindling due to repeated injections of lidocaine in animals, stable behavioral changes arise [12]. Hence the importance of studying whether pharmacologic kindling can develop as a re- sult of administration of other epileptogens, differing in the mechanism of their convulsant action from metrazol and lidocaine, and also of studying changes arising under these circum- stances in behavior. ~ The work was devoted to a study of the development of epileptic activ- ity (EpA) in rats during chronic administration of subconvulsive doses of picrotoxin, whose epileptogenic effect is linked with its action on the GABA-ionophore complex [13], and also to a study of behavioral disorders arising under these conditions. EXPERIMENTAL METHOD Experiments were carried out on male Wistar rats weighing 170-250 g. Each group consisted of no fewer than i0 animals. Picrotoxin, in doses of 5, 2.5, 1.5, or 1.25 mg/kg was injected intraperitoneally in a volume of 0.5 ml of 0.9% NaCI solution daily under identical conditions (the same time of day, in a room with the same intensity of illumination and with the same intensity of illumination and with the same noise effect). Animals of the control group re- ceived injections of physiological saline under identical conditions. The animals were ob- served for 90 min after receiving the injection of picrotoxin. The intensity of the seizures was expressed in points [3]. The latent period of the first seizure responses and of general- ized convulsions also was determined. Defensive responses were evaluated in accordance with the character of the animals' behavior when attempts were made to handle them, and these also were expressed in points [12]. To investigate the electrical activity of the brain, rats were anesthetized with hexobarbital (i00 mg/kg) and monopolar constantan electrodes were inserted into the hippocampus, caudate nucleus, sensomotor cortex, and cortex of the cerebellar vermis~ stereotaxically taking coordinates from the atlas [ii]; the reference electrode was fixed in the nasal bones. The results were subjected to statistical analysis [7]. EXPERIMENTAL RESULTS Injection of picrotoxin (5 mg/kg) caused generalized convulsions or spasms of the fore- limbs (the intensity of the convulsions was 3.6 • 0.2 points). After injection of picrotoxin in a dose of 2.5 mg/kg clonic convulsions were observed in eight of the 12 animals (1.8 • 0.7 points), whereas in a dose of 1.5 mg/kg spasms were observed in four of the 12 rats (0.3 • 0.2 points). After injection of picrotoxin in a dose of 1.25 mg/kg no seizure responses were observed. This dose was chosen for chronic administration. *Academician of the Academy of Medical Sciences of the USSR. Laboratory of General Pathology of the Nervous System, Institute of General Pathology and Pathological Physiology, Academy of Medical Sciences of the USSR, Moscow. Department of Pathologi- cal Physiology, N. I. Pirogov Odessa Medical Institute. Translated from Byulleten' Eksperimental' no• Biologii i Meditsiny, Vol. 108, No. 7, pp. 18-21, July, 1989. Original article submitted Octo- ber I, 1988. 0007-4888/89/0007-0923512.50 9 1989 Plenum Publishing Corporation 923