Physiology&Behavior,Vol. 22, pp. 701-705. PergamonPress and BrainResearch Publ., 1979. Printedin the U.S.A.
Avoidance of and Anticipatory Responses to Shock in Prenatally X-Irradiated Rats YOSHITAKA TAMAKP AND MINORU INOUYE 2
Department o f Physiology and Department of Embryology Institute for Developmental Research, Aichi Prefectural Colony Kasugai, Aichi 480-03, Japan ( R e c e i v e d 23 F e b r u a r y 1978) TAMAKI, Y. AND M. INOUYE. Avoidance of and anticipatory responses to shock in prenatally X-irradiated rats. PHYSIOL. BEHAV. 22(4)701-705, 1979.--Male MPI albino rats were exposed to X-irradiation in utero at a single dose of 200 R on Day 17 of gestation. This experiment was aimed to determine just how irradiated rats could differ from controls in a shuttlebox avoidance response. Irradiated rats had a significantly higher anticipatory response to CS which predicts shock, and also made a significantly higher incidence of consecutive anticipatory responses during the CS-US interval. Thus, facilitated avoidance behavior in irradiated rats is probably a consequence of a strong tendency to running induced by shock in shuttlebox. Since cell destruction caused by irradiation was evident in the primordial hippocampus, a smaller hippocampus developed. The dendrites of pyramidal neurons in Ammon's horn were abnormally oriented. Behavioral changes in shuttlebox after irradiation may be related to the hippocampus abnormality, based on stress-arousal interpretation of hippocampal functioning in a situation employing noxious stimulation. Prenatal X-irradiation Avoidance response
Irradiation Microcephalia Hippocampus Anticipatory response Shuttlebox
AN EXTENSIVE literature exists concerning behavioral changes and growth reductions in prenatally X-irradiated rodents. In the shuttlebox avoidance conditioning, for example, acute high doses (200-320 R) of irradiation facilitated avoidance behavior [9-11, 23], but chronically low levels (total 36 R) interfered with avoidance response [20]. These results in avoidance behavior might be produced by the changes in the pathological characteristics of the central nervous system after irradiation, since this pathogenic agent could result in different proliferating cell populations due to interference with DNA synthesis and mitosis [12]. In our previous study [22], we found that all rats exposed to 200 R on Day 17 of gestation showed microcephalia consisting of small cerebral hemispheres and poor hippocampal formation. The present study was undertaken to investigate the effect of exposure to an acute high-irradiation dose upon rat avoidance behavior in a shuttlebox. In order better to understand the nature of this effect the signaled escape condition [6], in which the avoidance contingency is absent but the escape contingency is present, was used to measure the incidence of the anticipatory response which occurred during the CS-US interval. The frequency of anticipatory responses to shock might provide an effective means to interpret facilitated avoidance behavior in irradiated rats. We also
Hippocampus abnormality
undertook to examine brain abnormality histologically in detail after irradiation. This histological observation would presumably aid us in assessing the nature of the relationship between avoidance performance and possible pathological defects. METHOD
Animals Albino rats of the commercially supplied MP1 strain from a closed colony were used. They were maintained on a 12-hr light-dark cycle in a temperature (23 -+ I°C) and humidity (55 +- 5%) controlled room. The virgin females were mated overnight with males, and the day on which copulation plugs were found is referred to as Gestation-Day 0. These females were exposed on Day 17 of gestation to a single dose of 200 R. A deep therapy 200 kVp X-ray machine was operated at 15 mA with 0.5 mm A1 and 0.5 mm Cu filtration (HVL 12.7 mm A1) at a target distance of 70 cm. The exposed rate was 25.7 R/min measured by Victoreen dosimeter, Some females were put to death 1 or 2 days after irradiation, then the fetuses were removed and fixed in Bouin's solution for microscopic examination of the brain. Other females were allowed to give birth and to rear their litters. Male offspring were housed in groups 3--4 after weaning at 21 days of age and received food and water ad lib.
~Now at Shinshu University. 2The authors are indebted to Mr. M. Kawabata, for his technical help with the irradiation, and to Professor H. Imada, Kwansei Gakuin University, for his extensive review of the manuscript. Address request for reprints to YT, Faculty of Education, Shinshu University, Nishinagano, Nagano 380, Japan.
C o p y r i g h t © 1979 B r a i n R e s e a r c h P u b l i c a t i o n s Inc.--0031-9384/'/9/040701-05502.00/0
702
TAMAKI AND INOUYE
Fifty-five male offspring, 26 fetallY irradiated and 29 nonirradiated, were tested when they were approximately 95 days of age. Average body weight was 198.9 __ 31.8 g (mean _+ SD) in irradiated and 249.9 -+ 33.9 g in controls; the difference was significant, t(53)=5.59, p
Avoidance of and Anticipatory Responses to Shock in Prenatally X-Irradiated Rats YOSHITAKA TAMAKP AND MINORU INOUYE 2
Department o f Physiology and Department of Embryology Institute for Developmental Research, Aichi Prefectural Colony Kasugai, Aichi 480-03, Japan ( R e c e i v e d 23 F e b r u a r y 1978) TAMAKI, Y. AND M. INOUYE. Avoidance of and anticipatory responses to shock in prenatally X-irradiated rats. PHYSIOL. BEHAV. 22(4)701-705, 1979.--Male MPI albino rats were exposed to X-irradiation in utero at a single dose of 200 R on Day 17 of gestation. This experiment was aimed to determine just how irradiated rats could differ from controls in a shuttlebox avoidance response. Irradiated rats had a significantly higher anticipatory response to CS which predicts shock, and also made a significantly higher incidence of consecutive anticipatory responses during the CS-US interval. Thus, facilitated avoidance behavior in irradiated rats is probably a consequence of a strong tendency to running induced by shock in shuttlebox. Since cell destruction caused by irradiation was evident in the primordial hippocampus, a smaller hippocampus developed. The dendrites of pyramidal neurons in Ammon's horn were abnormally oriented. Behavioral changes in shuttlebox after irradiation may be related to the hippocampus abnormality, based on stress-arousal interpretation of hippocampal functioning in a situation employing noxious stimulation. Prenatal X-irradiation Avoidance response
Irradiation Microcephalia Hippocampus Anticipatory response Shuttlebox
AN EXTENSIVE literature exists concerning behavioral changes and growth reductions in prenatally X-irradiated rodents. In the shuttlebox avoidance conditioning, for example, acute high doses (200-320 R) of irradiation facilitated avoidance behavior [9-11, 23], but chronically low levels (total 36 R) interfered with avoidance response [20]. These results in avoidance behavior might be produced by the changes in the pathological characteristics of the central nervous system after irradiation, since this pathogenic agent could result in different proliferating cell populations due to interference with DNA synthesis and mitosis [12]. In our previous study [22], we found that all rats exposed to 200 R on Day 17 of gestation showed microcephalia consisting of small cerebral hemispheres and poor hippocampal formation. The present study was undertaken to investigate the effect of exposure to an acute high-irradiation dose upon rat avoidance behavior in a shuttlebox. In order better to understand the nature of this effect the signaled escape condition [6], in which the avoidance contingency is absent but the escape contingency is present, was used to measure the incidence of the anticipatory response which occurred during the CS-US interval. The frequency of anticipatory responses to shock might provide an effective means to interpret facilitated avoidance behavior in irradiated rats. We also
Hippocampus abnormality
undertook to examine brain abnormality histologically in detail after irradiation. This histological observation would presumably aid us in assessing the nature of the relationship between avoidance performance and possible pathological defects. METHOD
Animals Albino rats of the commercially supplied MP1 strain from a closed colony were used. They were maintained on a 12-hr light-dark cycle in a temperature (23 -+ I°C) and humidity (55 +- 5%) controlled room. The virgin females were mated overnight with males, and the day on which copulation plugs were found is referred to as Gestation-Day 0. These females were exposed on Day 17 of gestation to a single dose of 200 R. A deep therapy 200 kVp X-ray machine was operated at 15 mA with 0.5 mm A1 and 0.5 mm Cu filtration (HVL 12.7 mm A1) at a target distance of 70 cm. The exposed rate was 25.7 R/min measured by Victoreen dosimeter, Some females were put to death 1 or 2 days after irradiation, then the fetuses were removed and fixed in Bouin's solution for microscopic examination of the brain. Other females were allowed to give birth and to rear their litters. Male offspring were housed in groups 3--4 after weaning at 21 days of age and received food and water ad lib.
~Now at Shinshu University. 2The authors are indebted to Mr. M. Kawabata, for his technical help with the irradiation, and to Professor H. Imada, Kwansei Gakuin University, for his extensive review of the manuscript. Address request for reprints to YT, Faculty of Education, Shinshu University, Nishinagano, Nagano 380, Japan.
C o p y r i g h t © 1979 B r a i n R e s e a r c h P u b l i c a t i o n s Inc.--0031-9384/'/9/040701-05502.00/0
702
TAMAKI AND INOUYE
Fifty-five male offspring, 26 fetallY irradiated and 29 nonirradiated, were tested when they were approximately 95 days of age. Average body weight was 198.9 __ 31.8 g (mean _+ SD) in irradiated and 249.9 -+ 33.9 g in controls; the difference was significant, t(53)=5.59, p
