Handbook of Behavioral Teratology

This book was developed in response to a need in behavioral teratology for a comprehen­ sive set of reviews of the field's many topics brought together in a single source. This volume represents the first effort to synthesize and integrate research in the field since 1969 when Justin Joffe wrote Prenatal Determinants of Behaviour. Joffe's book became a standard reference for many years, particularly for the experimental design of animal investigations. It has become increasingly evident, however, that some aspects of design once considered inviolate have changed and become part of a more flexible approach. In current research the emphasis is on a set of prioritized, but focused, experimental ques­ tions rather than on designs which factor all possible variables into every experiment. Also, new design considerations have arisen over the last 15 years, not appreciated when Joffe wrote. Moreover, the sheer volume of new experimental evidence generated since 1969 has increased the content of the field several fold. These considerations made a new review and critical appraisal of the field compelling. The book is divided into four major sections. Part I contains four chapters. These chapters provide discussions of the general principles of behavioral teratogenesis, and information on the historical, governmental, and methodological contexts in which the field operates. The purpose of these chapters is to provide the framework within which the review chapters in the remainder of the book may best be understood.

I General Principles and Issues.- 1 · Origins of Behavioral Teratology.- 1. Introduction.- 2. Emergence of Behavioral Teratology.- 3. Reemergence of Behavioral Teratology.- 4. Behavioral Teratology and Behavioral Toxicology.- 5. The Prenatal/Postnatal Dichotomy.- 6. Dual Influence of Regulations and the Fetal Alcohol Syndrome.- 6.1. Influence of Government Regulations.- 6.2. Influence of Discovery of the Fetal Alcohol Syndrome.- 7. Collaborative Project on Behavioral Teratology Methods.- 8. Other Influences.- 9. Scope of the Problem, or Who Cares Anyway?.- 10. Concluding Remarks.- 11. References.- 2 · Principles of Behavioral Teratology.- 1. Introduction.- 2. Wilson’s Principles of Teratology.- 2.1. Principle of Genetic and Environmental Determination.- 2.2. Principle of Critical Periods.- 2.3. Principle of Specific Mechanisms.- 2.4. Principle of Teratogenic Response.- 2.5. Principle of Target Access.- 2.6. Principle of Dose-Response Relationships.- 3. Principles of Behavioral Teratology.- 3.1. Principle of Genetic Determination.- 3.2. Principle of Critical Periods.- 3.3. Principle of Specific Mechanisms.- 3.4. Principle of Behavioral Teratogenic Response.- 3.5. Principle of Target Access.- 3.6. Principle of Dose-Response Relationships.- 3.7. Principle of Environmental Determination.- 3.8. Principle of Types of Behavioral Teratogens.- 3.9. Principle of Response Relationships.- 3.10. Principle of Maximum Susceptibility.- 3.11. Principle of Limits of Behavioral Teratogenic Susceptibility.- 3.12. Principle of Preconceptional and Transgenerational Effects.- 4. Behavioral versus Physical Teratogenesis.- 5. Concluding Remarks.- 6. References.- 3 · Comparison and Critique of Government Relations for Behavioral Teratology.- 1. Introduction.- 1.1. The Mandate.- 1.2. A Comparison.- 1.3. Logic or Fallacy?.- 2. Description and Critique of Regulations in Japan.- 3. Description and Critique of Regulations in Great Britain.- 4. Description and Critique of Regulations in France and Italy.- 5. Regulations of the European Economic Community.- 6. Summary of the Critique of Existing Guidelines.- 7. Description and Critique of Regulations in the United States.- 7.1. Overview.- 7.2. Food and Drug Administration Guidelines.- 7.3. Environmental Protection Agency Guidelines.- 8. Conclusions.- 9. References.- 4 · Methods in Behavioral Teratology.- 1. Introduction.- 2. General Experimental Design: Considerations for Increasing the Sensitivity of the Experiment.- 2.1. Procedures for the Reduction of Error Variance.- 2.2. Determination of the Appropriate Sample Size for Postnatal Testing.- 2.3. The Use of a Replicate Design.- 3. Guidelines for the Selection of Methods.- 3.1. When Human Behavioral Teratology Data Are Available.- 3.2. When Neurochemical, Neuroanatomical, or Animal Behavioral Data Are Available.- 3.3. When Information Is Not Available.- 4. Glossary of Methods That Are Frequently Used in Behavioral Teratology Studies.- 4.1. Measures of Learning Abilities.- 4.2. Measures of Sensory Function.- 4.3. Measures of Activity.- 4.4. Measures of Pharmacological Responsiveness.- 4.5. Measures of Neuromotor Abilities.- 5. Interpretation of Results.- 6. References.- II Drugs.- 5 · Behavioral Teratology of Alcohol.- 1. Introduction.- 2. Procedural Considerations.- 3. Behavioral Effects of Prenatal Alcohol Exposure.- 3.1. Suckling Behavior.- 3.2. Developmental Indices.- 3.3. Activity and Exploration.- 3.4. Learning.- 3.5. Sexually Dimorphic Behaviors.- 3.6. Aggression.- 3.7. Ethanol Preference, Sensitivity, and Tolerance.- 3.8. Reactivity and Seizure Susceptibility.- 4. Psychopharmacological Aspects of Behavioral Dysfunctions.- 5. Organizing Theories and Mechanisms.- 6. Summary.- 7. References.- 6 · Neurobehavioral Effects in Human and Animal Offspring following Prenatal Exposure to Methadone.- 1. Introduction.- 2. Neurobehavioral Effects in Infants and Children.- 2.1. Neonatal Sleep Studies.- 2.2. The Neonatal Abstinence Syndrome.- 2.3. Abstinence Mechanisms.- 2.4. Longitudinal Studies.- 2.5. Interpretation of Clinical Outcome: Multifactorial Causation.- 2.6. Effects on Mother-Infant Interaction.- 2.7. Genetic-Environmental Interactions.- 3. Animal Studies.- 3.1. Methodological Issues.- 3.2. Neurobehavioral Studies.- 3.3. Biochemical Effects on Growth.- 3.4. Neonatal Abstinence.- 3.5. Long-term Behavioral Effects.- 4. Summary and Conclusion.- 5. References.- 7 · Postnatal Functional Assessment following Central Nervous System Stimulant Exposure: Amphetamine and Caffeine.- 1. The Amphetamines.- 2. Caffeine.- 3. Conclusions.- 4. References.- 8 · Behavioral, Psychopharmacological, and Neurochemical Effects of Chronic Neuroleptic Treatment during Development.- 1. Behavioral Effects of Chronic Neuroleptic Treatment Early in Life.- 2. Psychopharmacological and Neurochemical Effects of Chronic Neuroleptic Treatment Early in Life.- 2.1. Alterations in the Dopaminergic System.- 2.2. Alterations in Other Neural Systems.- 3. Longevity of the Effects of Early Chronic Administration of Neuroleptics and the Importance of Age at the Time of Testing.- 4. Summary, Conclusions, and Possible Therapeutic Implications.- 5. References.- 9 · Behavioral Effects of Antimitotic Agents Administered during Neurogenesis.- 1. Introduction.- 2. Neuroteratology.- 3. Behavioral Effects.- 3.1. Seizures.- 3.2. Activity.- 3.3. Locomotor and Reflex Measures.- 3.4. Maze Tasks and Other Learning Problems.- 4. Birth Weight and Growth.- 5. References.- 10 · Behavioral Teratology of Anticonvulsant and Antianxiety Medications.- 1. Introduction.- 2. Anticonvulsants and Malformations.- 3. Fetal Anticonvulsant Syndromes.- 3.1. The Fetal Hydantoin Syndrome.- 3.2. The Fetal Trimethadione Syndrome.- 3.3. The Fetal Barbital and Primidone Syndromes.- 3.4. Comparisons among Fetal Anticonvulsant Syndromes.- 3.5. Fetal Effects of Valproate.- 3.6. Fetal Effects of Carbamazepine.- 3.7. Other Anticonvulsants.- 4. Psychoteratogenesis of Anticonvulsants in Animals.- 4.1. Psychoteratogenesis of Phenytoin.- 4.2. Psychoteratogenesis of Trimethadione.- 4.3. Psychoteratogenesis of Valproate.- 4.4. Psychoteratogenesis of Carbamazepine.- 5. Psychoteratogenesis of Benzodiazepines in Animals.- 6. Conclusions.- 7. References.- 11 · Prenatal Phenobarbital: Effects on Pregnancy and Offspring.- 1. Introduction.- 2. Barbiturate Use during Pregnancy.- 2.1. Use as a Sedative.- 2.2. Use as an Abused Substance.- 2.3. Use in Hyperbilirubinemia.- 2.4. Use as an Antiepileptic Agent.- 3. Distribution of Maternal Barbiturates and Effects on the Fetus.- 4. Prenatal Maternal Barbiturate Effects on Human Offspring.- 5. Procedural Problems with Animal Studies on Perinatal Phenobarbital.- 5.1. Drug Dose and Exposure Time.- 5.2. Effect of Route of Drug Administration on Pregnancy.- 5.3. Pre- versus Postnatal Contributions of Prenatal Phenobarbital.- 6. Prenatal Maternal Phenobarbital Effects on Animal Offspring Behavior.- 6.1. Developing Offspring.- 6.2. Mature Offspring.- 7. Possible Mechanisms Mediating the Behavioral Effects of Prenatal Phenobarbital.- 7.1. Effects on Endocrine Systems.- 7.2. Effects on the Central Nervous System.- 8. Summary and Conclusions.- 9. References.- 12 · The Effects of Early Marijuana Exposure.- 1. Introduction.- 2. Pharmacology.- 3. Methodological Caveats.- 4. Teratogenic Effects.- 5. Growth.- 6. Behavioral Teratology of Marijuana.- 6.1. Human Studies.- 6.2. Animal Studies.- 7. Conclusions.- 8. References.- III Environmental Agents.- 13 · Animal Models of Behavioral Effects of Early Lead Exposure.- 1. Introduction.- 2. Activity.- 2.1. Rat Studies.- 2.2. Mouse Studies.- 2.3. Motor Ability.- 2.4. Summary of Activity Studies.- 3. Learning.- 3.1. Avoidance Behavior.- 3.2. Maze Learning.- 3.3. Discrimination Learning.- 3.4. Schedule-Controlled Behavior.- 3.5. Learning in Nonhuman Primates.- 3.6. Summary of Learning Studies.- 4. Social Behavior.- 4.1. Mother-Infant Interaction.- 4.2. Interaction with Peers.- 5. Sensory Systems.- 5.1. Vision.- 5.2. Audition.- 6. Consummatory Behavior.- 7. Seizures and Stress.- 8. Conclusions.- 9. References.- 14 · Behavioral Teratogenesis Resulting from Early Cadmium Exposure.- 1. Introduction.- 1.1. Cadmium in the Environment.- 1.2. General Toxicity.- 1.3. Sensitivity of the Young to Early Cadmium Exposure.- 2. Prenatal Studies.- 2.1. Neurotoxic Effects.- 2.2. Oral Cadmium Exposure.- 2.3. Cadmium Exposure via Inhalation.- 3. Postnatal Exposure Studies.- 3.1. Cadmium Exposure via Parenteral Administration.- 3.2. Oral Cadmium Exposure.- 4. Effects of Male Cadmium Exposure on Progeny.- 5. Conclusions and Future Considerations.- 5.1. Summary.- 5.2. Development of a Standard Exposure Index.- 5.3. Role of Metallothionein.- 5.4. Interaction of Cadmium with Essential Metals.- 6. References.- 15 · Psychogenic and Neurogenic Abnormalities after Perinatal Insecticide Exposure: A Critical Review.- 1. Introduction.- 2. Aims: Assessment of Psychogenic and Neurogenic Abnormalities.- 3. Evaluation Criteria and Scope.- 4. Organochlorines.- 4.1. Background.- 4.2. Categorization.- 4.3. Biotransformation and Mode of Action.- 4.4. Placental and Lactational Transfer.- 4.5. Psychogenic and Neurogenic Abnormalities.- 5. Organophosphates.- 5.1. Background.- 5.2. Categorization.- 5.3. Biotransformation and Mode of Action.- 5.4. Placental or Lactational Transfer.- 5.5. Psychogenic and Neurogenic Abnormalities.- 6. Carbamates.- 6.1. Background.- 6.2. Categorization.- 6.3. Biotransformation and Mode of Action.- 6.4. Placental and Lactational Transfer.- 6.5. Psychogenic and Neurogenic Abnormalities.- 7. Conclusions.- 8. Future Trends and Comments.- 9. References.- 16 · Behavioral Teratology of Industrial Solvents.- 1. Introduction.- 1.1. Teratology Testing.- 1.2. Criteria for Evaluating Behavioral Teratology Studies.- 2. Behavioral Teratogenic Effects of Individual Solvents.- 2.1. Benzene (Postnatal).- 2.2. Carbon Disulfide.- 2.3. Chloroform.- 2.4. 2-Ethoxyethanol.- 2.5. Formaldehyde.- 2.6. 2-Methoxyethanol.- 2.7. Methyl Chloroform.- 2.8. Methyl n-Butyl Ketone (MnBK).- 2.9. Methylene Chloride.- 2.10. Paint Thinner (Postnatal Exposure).- 2.11. Perchlorethylene.- 2.12. Tertiary Butanol.- 3. Concluding Remarks.- 4. References.- IV Special Agents.- 17 · Maternal Mediation of the Effects of Malnutrition.- 1. Introduction.- 2. Prenatal Period.- 2.1. Normal Development.- 2.2. Effects of Malnutrition.- 2.3. Adaptations to Malnutrition.- 2.4. Summary.- 3. Postnatal Period.- 3.1. Normal Development.- 3.2. Effects of Malnutrition.- 3.3. Adaptations to Malnutrition.- 3.4. Summary.- 4. Discussion.- 5. References.- 18 · Perinatal Hypoxia: Implications for Mammalian Development.- 1. Introduction.- 2. Pending Issues.- 3. Pharmacokinetic and Physiological Factors.- 4. Gross Developmental Abnormalties.- 5. Early Behavioral Development.- 5.1. Prenatal Studies.- 5.2. Neonatal Studies.- 5.3. Summary.- 6. Motor Activity.- 6.1. Prenatal Studies.- 6.2. Neonatal Studies.- 6.3. Summary.- 7. Learning and Memory.- 7.1. Prenatal Studies.- 7.2. Neonatal Studies.- 7.3. Summary.- 8. References.- 19 · Effects of Prenatal Irradiation on Postnatal Psychophysiological Development.- 1. Introduction.- 2. The Nature of Ionizing and Nonionizing Radiation.- 3. Review of the Literature.- 3.1. Ionizing Radiation.- 3.2. Nonionizing Radiation.- 4. Conclusions.- 5. References.- 20 · Behavioral Teratogenicity of Gonadal and Adrenal Steroids.- 1. Introduction.- 2. Androgens.- 2.1. Reproductive Activity.- 2.2. Aggression.- 2.3. Play.- 2.4. Activity.- 2.5. Taste Preference.- 2.6. Acquired Behavior.- 3. Estrogens.- 3.1. Reproductive Activity.- 3.2. Aggression.- 3.3. Activity.- 3.4. Human Behavior and Personality.- 4. Progestins.- 4.1. Reproductive Activity.- 4.2. Activity.- 4.3. Acquired Behavior.- 4.4. Play.- 4.5. Human Behavior and Personality.- 5. Adrenal Corticosteroids.- 5.1. Developmental-Behavioral Milestones.- 5.2. Reproductive Activity.- 5.3. Aggression.- 5.4. Activity.- 5.5. Acquired Behavior.- 6. Concluding Comments.- 7. References.