Exploratory behavior, learning ability, and thyroid hormonal responses to stress in female rats rehabilitating from postnatal hypothyroidism

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Abstract
Newborn female Long-Evans rats were divided into groups of normal, hypothyroid [0.1% propylthiouracil (PTU) a reversible antithyroid goitrogen in the litter's drinking water], and hypothyroid rehabilitated (PTU water from birth to day 25, normal water thereafter). The rats were tested for several adaptive behavioral tasks between 40 and 90 days of age. At day 50, serum concentration of TSH and thyroid hormones revealed no detectable amounts of T4 and a 10-fold increase in TSH in the hypothyroid rats. At the same age in the rehabilitated animals, TSH levels were still below normal, a deficit fully normalized by day 90. Normal 50-day-old rats responded to pain stress (electric footshocks) by a significant depression of serum T4 and elevation of T3 levels within 10 min of treatment, whereas the rehabilitated animals exhibited an opposite pattern of response, i.e., an increase in the circulating T4 and a decrease in T3. At 50 days of age, both hypothyroid and rehabilitated rats showed decreased exploratory activity and no habituation in the hole-board test, whereas the locomotor activity of the rehabilitated females was significantly higher than that of the normals. No differences were found in the scores of passive avoidance learning (one trial step-through) among the three groups. Similarly, the rate of acquisition of the active one-way conditioned avoidance response (CAR) of the hypothyroid and rehabilitated rats did not differ significantly from that of the controls. However, the hypothyroid rats required significantly more unconditioned stimuli (footshocks) to acquire CAR and showed longer response latency and less intertrial responses. Although the hypothyroid rats showed no extinction of CAR, the rehabilitated rats were capable of extinction to an extent indistinguishable from normal rats. But compared with the normal animals, the rehabilitated rats showed significantly higher intertrial activity during both the acquisition and extinction phases of CAR.