title: Postnatal haloperidol eliminates the deficit in circling behavior produced by prenatal exposure to the same drug.
abstract: Up to 35% of pregnant women take psychotropic drugs at least once during gestation [Austin and Mitchell, 1998]. From concurrent animal and human evidence, it has been proposed that exposure to several psychoactive medications in utero or during lactation increases the risk for permanent brain disorders. Present preventive or therapy practices applied on humans for this type of long-lasting behavioral alterations are mainly based on empirical results. Here, we test an experimental approach designed to counteract a circling performance deficit that appears in Sprague-Dawley rats at puberty on exposure to the dopaminergic blocker haloperidol (HAL) during gestation [J.L. Brusés, J.M. Azcurra, The circling training: A behavioral paradigm for functional teratology testing, in: P.M. Conn (Ed.), Paradigms for the study of behavior, Acad. Press, New York, 1993, pp. 166-179. Method Neurosci. 14]. Gestational exposure to HAL (GD 5-18, 2.5 mg/kg/day ip) induced the expected circling activity decrease in the offspring at the fifth week of life. When prenatal exposure to HAL was continued through lactation (PD5-21, 1.5 mg/kg/day ip), rats otherwise showed a control-like circling performance. No difference was yet found between lactation-only, HAL-exposed pups and saline (SAL)-treated controls (n=8 each group). We further performed saturating (3H)-spiroperidol (SPI) binding assays on striatal P2 membrane fractions 2 months later. The dopamine-type D2-specific binding results suggested that above circling behavior findings could be partially explained by enduring HAL-induced neurochemical changes. The role of critical periods of sensitivity as transient windows for opportunistic therapies for behavioral teratology is discussed.
authors.affiliation: Interdisciplinary Project on Neuroteratology (IPON), Departamento de Biodiversidad y Biología Experimental, Facultad de Ciencias Exactas y Naturales, Ciudad Universitaria, Universidad de Buenos Aires, Argentina.
authors.forename: Marcelo Javier
authors.initials: MJ
authors.lastname: Wolansky
authors.forename: Mariano
authors.initials: M
authors.lastname: Soiza-Reilly
authors.forename: Mariana
authors.initials: M
authors.lastname: Fossati
authors.forename: Julio Marcos
authors.initials: JM
authors.lastname: Azcurra
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects; D018492:Dopamine Antagonists / Q000493:pharmacokinetics / Q000627:therapeutic use / Q000633:toxicity; D005260:Female; D006220:Haloperidol / Q000627:therapeutic use / Q000633:toxicity; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011869:Radioligand Assay / Q000379:methods; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013134:Spiperone / Q000493:pharmacokinetics; D013239:Stereotyped Behavior / Q000187:drug effects*; D019956:Stereotypic Movement Disorder / Q000139:chemically induced / Q000188:drug therapy*; D014316:Tritium / Q000493:pharmacokinetics
chemical_list: D018492:Dopamine Antagonists; D014316:Tritium; D013134:Spiperone; D006220:Haloperidol