Altered adult behavior of mice following postnatal treatment with haloperidol.
ABSTRACT Haloperidol (1 and 2 mg/kg) was administered SC daily to BALB/c and Swiss/Webster mice from postnatal days 4 through 21. Non consistent statistically significant drug effects were detected on growth and reflex development. Spontaneous motor activity increased significantly in both sexes of the Swiss/Webster outbred strain, and in the Balb/c males. Performance of a fixed ratio schedule of reinforcement of both male and female haloperidol-exposed mice was not statistically different from control performance. Interpretation of such data must take into account the sensitivity of the testing devices, the effects of repeated testing of a single animal, and the suitability of traditional statistical methods in developmental pharmacology and toxicology.
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ABSTRACT: During pregnancy and lactation, women often receive medications that have CNS activity. However, the developmental consequences for infants of perinatal exposure to these medications have not been fully characterised. Some CNS drugs are associated with congenital anomalies and delayed development. An obvious dilemma arises for clinicians, since maternal benefits of pharmacotherapy must be judiciously weighed against risk to the infant. Treatment plans should be directed to the individual needs of the mother and child, in addition to enhancing safety for the dyad. Preclinical studies have demonstrated long term effects of CNS drugs on neuro-development, yet findings are limited on similar risks in humans. In general, clinical information has been gleaned from case reports and uncontrolled studies. Therefore, healthcare providers are burdened with the responsibility of making clinical decisions with minimal data. One solution for enhancing decision-making is to appreciate underlying principles applicable to the evaluation of neurodevelopmental protocols. If the objective is to evaluate developmental effects of CNS drugs, paradigms should address basic tenets of neurodevelopment and drug disposition. Factors related to the general condition of the mother are often neglected. Frequently the data on dose, duration and period of drug exposure are incomplete. Since systematic follow-up assessments generally are not performed, subtle effects on mental acuity and behaviour may have been missed. These methodological deficiencies suggest that further investigation is warranted. Nonetheless, some data on the potential for persistent effects are available. Antidepressants taken during pregnancy and lactation do not appear to be teratogenic or associated with acute adverse effects, but data on development are inadequate. On the other hand, delayed motor development was reported following administration of benzodiazepines during gestation. Adverse effects have not been found from lactational exposure to benzodiazepines, but caution is advised because of potential accumulation in infants. Effects on development and learning were linked to in utero exposure to anticonvulsants. Finally, delays in development were reported in children exposed to antipsychotics in breast milk. Because of teratogenic risks associated with CNS medications, exposed infants should be carefully monitored.CNS Drugs 12(6). DOI:10.2165/00023210-199912060-00004 · 4.38 Impact Factor
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ABSTRACT: The long term behavioural and biochemical effects of chronic chlordiazepoxide treatment during the period of neuronal maturation in the rat have been investigated. The administration to lactating mothers of chlordiazepoxide at very low doses (0.22 and 2.6 mg/kg) in their drinking water affects both behavioural and biochemical parameters in offspring at 60 days of age and undrugged since weaning. A deficit in the acquisition of the conditioned avoidance response in treated rats was observed, although no significant difference in spontaneous locomotor activity between control and treated rats was found. 3H-Flunitrazepam binding sites in cerebral cortex and hippocampus were decreased by the treatment, whereas no change was detected in cerebellum. Moreover, 3H-muscimol binding sites increased in hippocampus with no changes in cerebral cortex and cerebellum. According to the different regional distribution of benzodiazepine type 1 and type 2 receptors, we suggest that type 2 receptors are selectively affected by the treatment, and that the GABAergic receptor system is also permanently altered by administration of chlordiazepoxide during early postnatal life.Psychopharmacology 02/1983; 81(3):261-6. DOI:10.1007/BF00427275 · 3.99 Impact Factor
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ABSTRACT: The assessment of behavioral changes produced by prenatal or early postnatal exposure to potentially noxious agents requires both the designing of ad hoc tests and the adaptation of tests for adult animals to the characteristics of successive developmental stages. The experience in designing tests is still more limited than in the adaptation of tests, but several tests have already proven their usefulness; some examples are the suckling test, the homing test, and evaluations of dam-pup and pup-pup interactions. Functional observational batteries can exploit the development at specified postnatal ages of several reflexes and responses that are absent at birth in altricial rodent species with a short pregnancy such as the rat and the mouse. In neonates, the assessment of early treatment effects can rely not only on deviations from normal responding but also on changes in the time of appearance of otherwise normal response patterns. The same applies to other end points such as responses to pain and various types of spontaneous motor/exploratory activities, including reactivity to a variety of drug challenges that can provide information on the regulatory systems whose development may be affected by early treatments. In particular, the analysis of ontogenetic dissociations (i.e., differential early treatment effects depending jointly on developmental stage at the time of exposure, age of testing, and response end point) can be of considerable value in the study of treatments' mechanisms of action. Overall, it appears that behavioral teratological assessments can be effectively used both proactively, i.e., in risk assessment prior to any human exposure, and reactively. In the latter case, these assessments could have special value in the face of agents suspected to produce borderline changes in developing humans, whose innocuousness or noxiousness can be difficult to establish in the absence of hard evidence of teratogenicity.Environmental Health Perspectives 05/1996; 104 Suppl 2(Suppl 2):285-98. DOI:10.2307/3432648 · 7.03 Impact Factor