Influences of early thyroid hormone manipulations: delays in pup motor and exploratory behavior are evident in adult operant performance.

The effects of thyroid hormone depletion and enhancement on litter size, survival, body mass, ambulation, quadrant crossing, home orientation, day of eye opening, and free serum T3 and T4 levels were examined in Study 1. In Study 2, the effects of the timing of prenatal insult and the level of thyroid hormone depletion on litter size, survival, body mass, and free serum T3 and T4 levels were examined. Upon the completion of Study 1, randomly selected pups were maintained on ad-libitum water and food for 2 years, and performance was evaluated on fixed and variable ratio schedules, fixed and variable interval schedules, and probability and reversal learning tasks (Study 3). In Study 4, human subjects diagnosed with and treated for either congenital hypothyroidism or congenital hyperthyroidism were tested on the operant procedures used in Study 3, as well as on a series of simple reaction time, serial timing, and conjunctive and disjunctive search tasks. Dose-dependent decreases in survival and delays in the presentation of early motor and exploratory skills were observed following thyroid hormone depletion; dose-dependent accelerations in the presentation of early motor and exploratory skills were observed following thyroid hormone enhancement. Pups that had been prenatally exposed to propylthiouracil (PTU) 1-2 years after the return of thyroid hormones to baseline levels were significantly less accurate at timing on fixed and variable interval schedules, demonstrated an inability to allocate responding on probability tasks, and committed more errors during original learning (OL) and on each reversal problem. Similar deficits were observed in follow-up tests with humans diagnosed with congenital hypothyroidism, as were deficits in serial timing and visual searching. Collectively, the present results demonstrate that the pervasive and negative effects of prenatal thyroid deficiency on early behavior are also expressed during adult operant performance.