Abstract
The possibility that the exposure of the embryo to certain chemical substances can lead to behavioral disturbances is known from human epidemiological studies, e.g., in chronic poisoning with mercury and ethanol. Therefore, efforts are made to develop toxicological techniques with which new behavioral teratogens can be recognized.
The review describes the most important experimental methods which are presently explored, and which are based on a rich body of knowledge accumulated by experimental psychologists. Most of the tests were developed with small animals, mostly with rats. They range from a rather straightforward determination of various reflexes to complex behavioral situations involving mechanical devices, operant conditioning techniques and procedures evaluating social behavior.
In applying these methods in routine toxicology, it is important to remember, that many behavioral effects determined in newborn and adult animals are subtle. Moreover, they are influenced by a large variety of environmental factors affecting the health and the behavior of the mothers and of the offspring in the early and later phases of development. Therefore, the experiments must be conducted under highly standardized conditions and must be controlled rigorously. It is concluded that the best experimental strategy for the evaluation of potential behavioral teratogens is not yet established. Therefore, it would be premature to decide on a fixed protocol to be included in routine animal safety experiments for drugs and other chemical substances.
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References
Ader R, Conklin PM (1963) Handling of pregnant rats: effects on emotionality of their offspring. Science 142: 411–412
Alberts JR (1978) Huddling by rat pups: Group behavioral mechanisms of temperature regulation and energy conservation. J Comp Physiol Psychol 92: 231–245
Alder S, Zbinden G (1977) Methods for the evaluation of physical, neuromuscular and behavioral development of rats in early postnatal life. In: Neubert D, Merker HJ, Kwasigroch TE (eds) Methods in prenatal toxicology. Thieme, Stuttgart, pp 175–185
Altman J, Bulut FG (1976) Organic maturation and the development of learning capacity. In: Rosenzweig MR, Bennett EL (eds) Neural mechanisms of learning and memory. MIT Press, Cambridge MA, London, pp 236–240
Altman J, Sudarshan K, Das GD, McCormick N, Barnes D (1971) The influence of nutrition on neural and behavioral development: III. Development of some motor, particularly locomotor patterns during infance. Dev Psychobiol 4: 97–114
Amsel A, Burdette DR, Letz R (1976) Appetitive learning, patterned alternation, and extinction in 10-d-old rats with non-lactating suckling as reward. Nature 262: 816–818
Amsel A, Radek CC, Graham M, Letz R (1977) Ultrasound emission in infant rats as an indicator of arousal during appetitive learning and extinction. Science 197: 786–788
Archer JE, Blackman DE (1970) Prenatal psychological stress and offspring behavior in rats and mice. Dev Psychobiol 4: 193–248
Ardila R, Rezk M, Polanco R, Pereira F (1977) Early handling, electric shock, and environmental complexity: effects on exploratory behavior, “emotionality”, and body weight. Psychol Rev 2: 219–224
Baker JJ, Baker TB, Kesner RP (1977). Taste aversion learning in young and adult rats. J Comp Physiol Psychol 91: 1168–1178
Bornhausen M, Müsch HR, Greim H (1980) Operant behavior performance changes in rats after prenatal methylmercury exposure. Toxicol Appl Pharmacol 56: 305–310
Bornschein RL, Hastings L, Manson JM (1980) Behavioral toxicity in the offspring of rats following maternal exposure to dichlormethane. Toxicol Appl Pharmacol 52: 29–37
Broitman ST, Donoso AO (1978) Effects of chronic imipramine and clomipramine oral administration on maternal behavior and litter development. Psychopharmacology 56: 93–101
Bush M, Leathwood PD (1975) Effect of different regimens of early malnutrition on behavioral development and adult avoidance learning in Swiss white mice. Br J Nutr 33: 373–385
Butcher RE, Vorhees CV (1979) A preliminary test battery for the investigation of the behavioral teratology of selected psychotropic drugs. Neurobehav Toxicol [Suppl 1] 1: 207–212
Butcher RE, Brunner RL, Roth T, Kimmel CA (1972) A learning impairment associated with maternal hypervitaminosis-A in rats. Life Sci 11: 141–145
Cabe PA, Tilson HA, Mitchell CL, Dennis R (1978) A simple recording grip strength device. Pharmacol Biochem Behav 8: 101–102
Clark CVH, Gorman D, Vernadakis A (1970) Effects of prenatal administration of psychotropic drugs on behavior of developing rats. Dev Psychobiol 3: 225–235
Cornwell-Jones C, Sobrian SK (1977) Development of odor-guided behavior in Wistar and Sprague-Dawley rat pups. Physiol Behav 19: 685–688
Coyle IR, Singer G (1975) The interaction of post-weaning housing conditions and prenatal drug effects on behavior. Psychopharmacologie 41: 237–244
Davis WM, Lin CH (1972) Prenatal morphine effects on survival and behavior of rat offspring. Res Commun Chem Pathol Pharmacol 3: 205–214
Elsner J, Looser R, Zbinden G (1979) Quantitative analysis of rat behavior patterns in a residential maze. Neurobehav Toxicol [Suppl 1] 1: 163–174
Fechter LD, Annau Z (1977) Toxicity of mild prenatal carbon monoxide exposure. Science 197: 680–682
Fox WM (1965) Reflex ontogeny and behavioral development of the mouse. Anim Behav 3: 234–241
Furchtgott E, Echols M (1958) Locomotor coordination following pre-and neonatal X irradiation. J Comp Physiol Psychol 51: 292–294
Golub M, Kornetsky C (1974) Seizure susceptibility and avoidance conditioning in adult rats treated prenatally with chlorpromazine. Dev Psychobiol 7: 79–88
Grant LD (1976) Research strategies for behavioral teratology studies. Environ Health Perspect 18: 85–94
Gregg B, Kittrell EMW, Domjan M, Amsel A (1978) Ingestional aversion learning in pre-weanling rats. J Comp Physiol Psychol 92: 785–795
Herrenkohl LR, Whitney JB (1976) Effects of prepartal stress on postpartal nursing behavior, litter development and adult sexual behavior. Physiol Behav 17: 1019–1021
Hoffeld DR, Webster RL (1965) Effect of injection of tranquillizing drugs during pregnancy on offspring. Nature 205: 1070–1072
Hutchings DE (1967) Infantile body temperature loss in rats: effects of duration of cold exposure, rate of heat loss, level of hypothermia, and rewarming on later emotionality. Psychol Rep 21: 985–1002
Johanson IB, Hall WG (1979) Appetitive learning in 1-day-old rat pups. Science 105: 419–421
Kenny JT, Blass EM (1977) Suckling as incentive to instrumental learning in pre-weanling rats. Science 196: 898–899
Klaus S, Hacker E (1978) Die Entwicklung des Schwimmverhaltens bei Mäusen als Verhaltenstest in der Toxikologie. Z Versuchstierk 20: 81–87
Lamptey MS, Walker BL (1978) Learning behavior and brain lipid composition in rats subjected to essential fatty acid deficiency during gestation, lactation, and growth. J Nutr 108: 358–367
Lasky DI, Zagon IS, McLaughlin PJ (1977) Effect of maternally administered heroin on the motor activity of rat offspring. Pharmacol Biochem Behav 7: 281–284
Martin JC, Martin DC, Sigman G, Radow B (1978) Maternal ethanol consumption and hyperactivity in cross-fostered offspring. Physiol Psychol 6: 362–365
Müsch HR, Bornhausen M, Kriegel H, Greim H (1978) Methylmercury chloride induces learning deficits in prenatally treated rats. Arch Toxicol 40: 103–108
Noirot E (1972) Ultrasounds and maternal behavior in small rodents. Dev Psychobiol 5: 371–387
Okon EE (1972) Factors affecting ultrasound production in infant rodents. J Zool (Lond) 168: 139–148
Peters DP (1978) Effects of prenatal nutritional deficiency on affiliation and aggression in rats. Physiol Behav 20: 359–362
Pfeifer WD, Rotundo R, Myers M, Denenberg VH (1976) Stimulation in infancy: unique effect of handling. Physiol Behav 17: 781–784
Robertson RT, Majka JA, Peter CP, Bokelman DL (1980) Effects of prenatal exposure to chlorpromazine on postnatal development and behavior of rats. Toxicol Appl Pharmacol 53: 541–549
Rudy JW, Cheatle MD (1977) Odor aversion learning in neonatal rats. Science 198: 845–846
Sadile AG, Lat J, Cioffi LA (1977) Late effects of early postnatal malnutrition on habituation dynamics of spontaneous exploratory activity in adult rats. Activ Nerv Sup 19: 135–137
Salama AA, Hunt JMcV (1964) “Fixation” in the rat as a function of infantile shocking, handling, and gentling. J Gen Psychol 105: 131–162
Sales GD, Skinner NC (1979) The effect of ambient temperature on body temperature and on ultrasonic behavior in litters of albino laboratory mice deprived of their mothers. J Zool (Lond) 187: 165–281
Smart JL, Dobbing J (1971) Vulnerability of developing brain. II. Effects of early nutritional deprivation on reflex ontogeny and development of behaviour in the rat. Brain Res 28: 85–95
Smart JL, Whatson TS, Dobbing J (1977) Perseverative behavior by adult offspring of underfed mother rats. Activ Nerv Sup (Praha) 19: 128–129
Sobotka TJ, Cook MP, Brodie RE (1974) Effects of perinatal exposure to methylmercury on functional brain development and neurochemistry. Biol Psychiat 8: 307–320
Sobrian SK (1977a) Aversive prenatal stimulation: effects on behavioral, biochemical, and somatic ontogeny in the rat. Dev Psychobiol 10: 41–51
Sobrian SK (1977b) Prenatal morphine administration alters behavioral development in the rat. harmacol Biochem Behav 7: 285–288
Sobrian SK, Cornwell-Jones C (1977) Neonatal 6-hydroxytryptamine alters olfactory development. Behav Biol 21: 329–340
Spyker DA, Spyker JM (1977) Response model analysis for cross-fostering studies: prenatal versus postnatal effects on offspring exposed to methylmercury dicyanodiamide. Toxicol Appl Pharmacol 40: 511–527
Spyker JM (1975) Assessing the impact of low level chemicals on development: behavioral and latent effects. Fed Proc 34: 1835–1844
Spyker JM, Sparber SB, Goldberg AM (1972) Subtle consequences of methylmercury exposure: Behavioral deviations in offspring of treated mothers. Science 177: 621–623
Su MQ, Okita GT (1976) Behavioral effects on the progeny of mice treated with methylmercury. Toxicol Appl Pharmacol 38: 195–205
Vorhees CV, Brunner RL, Butcher RE (1979) Psychotropic drugs as behavioral teratogens. Science 205: 1220–1225
Walker S, Furchtgott E (1970) Effect of prenatal X-irradiation on the acquisition, extinction, and discrimination of a classically conditioned response. Radiat Res 42: 120–128
Weinberg J, Levine S (1977) Early handling influences on behavioral and physiological responses during active avoidance. Dev Psychobiol 10: 161–169
Werboff J, Havlena J (1962) Postnatal behavioral effects of tranquillizers administered to the gravid rat. Exp Neurol 6: 263–269
Werboff J, Kesner R (1963) Learning deficits of offspring after administration of tranquillizing drugs to the mothers. Nature 197: 106–107
Werboff J, Goodman I, Havlena J, Sikov MR (1961) Effects of prenatal X-irradiation on motor performance in the rat. Am J Physiol 201: 703–706
Werboff J, Havlena J, Sikov MR (1962) Effects of prenatal X-irradiation on activity, emotionality and maze-learning ability in the rat. Radiat Res 16: 441–452
Whatson TS, Smart JL (1978) Social behavior of rats following pre- and early postnatal undernutrition. Physiol Behav 20: 749–753
Whatson TS, Smart JL, Dobbing J (1975) Dominance relationships among previously undernourished and well fed male rats. Physiol Behav 14: 425–429
Winneke G, Brockhaus A, Baltissen R (1977) Neurobehavioral and systemic effects of long term blood-lead elevation in rats. I. Discrimination learning and open field-behavior. Arch Toxicol 37: 247–263
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Zbinden, G. Experimental methods in behavioral teratology. Arch Toxicol 48, 69–88 (1981). https://doi.org/10.1007/BF00310480
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DOI: https://doi.org/10.1007/BF00310480