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', 4, 4', 5-pentachlorobiphenyl (PCB126) on learning behavior in offspring.

Methods: Pregnant 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.

Fig. 1

Response rate (number of lever presses per minute) of male (left) and female (right) rat offspring born to dams exposed to either 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) or 3, 3′, 4, 4′, 5-pentachlorobiphenyl (PCB126) at three different doses in phases 1, 2 and 3 in the fixed ratio (FR) component. Doses of TCDD were 50, 200 and 800 ng/kg, respectively, and those of PCB126 were 500, 2,000 and 8,000 ng/kg, respectively. Open circle indicates control, empty, gray and black squares indicate 50, 200 and 800 ng/kg of TCDD, respectively, open, gray and black triangles indicate 500, 2,000 and 8,000 ng/kg of PCB126, respectively. Each symbol indicates the mean and SEM of number of lever presses in each ten-session phase. *p < 0.05 (vs. other groups)

Fig. 2

Response rate (number of lever presses per minute) of male (left) and female (right) rat offspring born to dams exposed to either TCDD or PCB126 at three different doses in phases 1, 2 and 3 in the differential reinforcement of low rates (DRL) component. Open circle indicates control, empty, gray and blacksquares indicate 50, 200 and 800 ng/kg of TCDD, respectively, and open, gray and black triangles indicate 500, 2,000 and 8,000 ng/kg of PCB126, respectively. Each symbol indicates the mean and SEM of a number of lever presses in each ten-session phase. *p < 0.05 (vs. other groups)

Fig. 3

Response rate (number of lever presses per minute) of male (upper) and female (lower) rat offspring born to dams exposed to either TCDD or PCB126 at three different doses in phases 1, 2 and 3 in the FR component. Doses of TCDD were 50, 200 and 800 ng/kg, respectively, and those of PCB126 were 500, 2,000 and 8,000 ng/kg, respectively. Open, black and gray bars indicate control, TCDD and PCB126, respectively. Bars indicate the mean and SEM of the number of lever presses in each ten-session phase. *p < 0.05 (vs. other groups)

Fig. 4

Response rate (number of lever presses per minute) of male (upper) and female (lower) rat offspring born to dams exposed to either TCDD or PCB126 at three different doses in phases 1, 2 and 3 in the DRL component. Doses of TCDD were 50, 200 and 800 ng/kg, respectively, and those of PCB126 were 500, 2,000 and 8,000 ng/kg, respectively. Open, black and gray bars indicate control, TCDD and PCB126 groups, respectively. Bars indicate the mean and SEM of the number of lever presses in each ten-session phase

Fig. 5

Reward rate (number of food reward per minute) of male (upper) and female (lower) rat offspring born to dams exposed to either TCDD or PCB126 at three different doses in the DRL component. Doses of TCDD were 50, 200 and 800 ng/kg, respectively, and those of PCB126 were 500, 2,000 and 8,000 ng/kg, respectively. Open, black and gray bars indicate control, TCDD and PCB126 groups, respectively. Bars indicate the mean and SEM of the number of food reward in each ten-session phase

Fig. 6

Response rate (number of lever presses per minute) at the last five sessions in FR component for male (upper left) and female (upper right) rat offspring and in DRL component for male (lower left) and female (lower right) in mult FR 20 DRL 20-s schedule. Open bar indicates response rate of control. The first three bars next to open bar: light gray, dark gray and black bars indicate response rates of low (50 ng/kg), medium (200 ng/kg), and high (800 ng/kg) doses of TCDD, respectively, and the next three bars: light gray, dark gray and black bars indicate those of low (500 ng/kg), medium (2,000 ng/kg) and high (8,000 ng/kg) doses of PCB126, respectively. Bars indicate the mean and SEM of number of lever press per minute. *p < 0.05