Learning behavior in rat offspring after in utero and lactational exposure to either TCDD or PCB126

Abstract

Objectives We studied and compared the possible effects of in utero and lactational exposure to 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) or 3, 3 0 , 4, 4 0 , 5-pentachlorobiphenyl (PCB126) on learning behavior in offspring. MethodsPregnant Long-Evans Hooded rats were administered either TCDD (50, 200, or 800 ng/kg) or PCB126 (500, 2,000 or 8,000 ng/kg) on gestational day 15. A procedure of schedule-controlled operant behavior was applied to examine learning behavior in the male and female offspring at 11 weeks of age for 30 days. Three indices, namely, response rates in a fixed ratio (FR) and in a differential reinforcement of low rates (DRL), and reward rate in the DRL component in multiple FR 20 DRL 20 s (mult-FR 20 DRL 20-s) test sessions, were used for the evaluation of learning behavior. Results Toxic effects on learning behavior in male and female pups following in utero and lactational exposure to TCDD or PCB126 were observed mainly in the FR learning component. However, no linear dose-dependent effects of either of the two compounds were observed for the above three indices. The response rates of animals in the low-dose TCDD and PCB126 groups decreased and those in medium-dose TCDD and PCB126 groups appeared to induce hyperactive behavior. The high dose of PCB126 appeared to have a distinct toxicity from that of TCDD in terms of the acquisition of learning behavior. Conclusions Toxicities of PCB126 and TCDD in learning behavior might be similar to each other and the current toxic equivalency factor (TEF) of 0.1 for PCB126 can be considered to be appropriate for this endpoint.

Executive Function Deficits and Social-Behavioral Abnormality in Mice Exposed to a Low Dose of Dioxin In Utero and via Lactation

“…However, in recent years, such a premise has been challenged by piles of evidence that shows the presence of non-monotonic modes of action of chemicals and hormones in a low-dose range and may elucidate the underlying mechanisms [84]. As the non-monotonic dose-response relationship found in this study was widely consistent among the indices of behavior and immunohistochemistry, the present results strongly suggest that TCDD is a chemical that can induce a non-monotonic dose-response effect on a systemic level, an observation that is consistent with previous studies on rat progeny [14], [19], [20]. To address mental disorders and related health problems as the endpoints of low-dose exposure of TCDD, further studies are required to clarify the non-monotonic association between a low dose of TCDD and its effects on the brain and behavior on both the molecular and systemic levels.…”

“…Clinical and epidemiological studies have revealed the occurrence of a variety of signs and symptoms in dioxin-exposed human populations, including disturbances in psychomotor and neurobehavioral functions in children [8], [9], [11]. In utero and lactational exposure of rodents to 2,3,7,8-tetrachlorodibenzo- p -dioxin (TCDD), the most toxic congener among dioxin family, induces abnormal sexually dimorphic behaviors in adulthood [12], [13], [14], [15], [16], [17], and alters learning behaviors [18], [19], [20], [21], [22], [23], [24], [25], [26]. Previous studies have shown that the cerebral cortex is a vulnerable target to TCDD insult.…”

In utero and lactational exposure to 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin modulates dysregulation of the lipid metabolism in mouse offspring fed a high‐calorie diet

“…However, when the TCDD dose is low and administered to pregnant dams, nearly all of the dioxin is eliminated from the body of the offspring at the time of analysis (Gasiewicz et al, 1983), with no overt signs of toxicity. It is interesting to note that different laboratories have also reported alterations in the higher brain functions of TCDDexposed rats and mice under such exposure conditions (Markowski et al, 2002;Widholm et al, 2003;Nishijo et al, 2007;Hojo et al, 2008). However, the mechanism of TCDDinduced neurotoxicity remains elusive.…”

Fetal exposure to 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin transactivates aryl hydrocarbon receptor‐responsive element III in the tyrosine hydroxylase immunoreactive neurons of the mouse midbrain

“…Administration of several endocrine disruptors to rats at 5 days of age also causes motor hyperactivity at 4-5 weeks of age, concomitant with a decrease in the gene expression of dopamine transporter DAT1 (Ishido et al, 2005). Fetal exposure to TCDD results in hyperactivity in rats (Hojo et al, 2008;Nishijo et al, 2007). Although the extracellular dopamine concentration and expression level of the dopamine transporters were not analyzed in the present study, our transgenic mice treated with TCDD may also have shown motor hyperactivity owing to an increment of dopaminergic input in the mesotelencephalic system arising from the enhanced expression of TH and increased number of TH-ir neurons.…”

“…In fact, epidemiological data have suggested that the serum concentration of dioxins and related compounds in children are associated with the likelihood of developing LD and ADD (Lee et al ., ). In agreement with these epidemiological findings, previous experimental studies have indicated that hyperactivity occur subsequent to fetal and lactational exposure to TCDD (Hojo et al ., ; Nishijo et al ., ).…”