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Attention-deficit and hyperactive neurobehavioural characteristics induced by perinatal hypothyroidism in rats
Takayuki Negishi1, Katsuyoshi Kawasaki, Satoshi Sekiguchi
1Department of Biomedical Science, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan. taka-u@yayoi-club.ne.jp
Insights
Perinatal hypothyroidism in rats induced by propylthiouracil (PTU) resulted in ADHD-like behaviors, including hyperactivity and impaired attention. These findings highlight thyroid hormone
Area of Science:
- Neuroendocrinology
- Developmental neuroscience
- Behavioral neuroscience
Background:
- Thyroid hormone is crucial for mammalian central nervous system (CNS) development.
- Thyroid system disruption during perinatal development can lead to lasting neurological effects.
Purpose of the Study:
- To investigate behavioral alterations in rats with transient perinatal hypothyroidism induced by propylthiouracil (PTU).
- To specifically examine attention-deficit/hyperactivity disorder (ADHD)-like behaviors in these rats.
Main Methods:
- Induction of transient perinatal hypothyroidism using propylthiouracil (PTU).
- Assessment of behavioral changes using a series of tests: open field test, passive avoidance test, active avoidance test, and spontaneous motor activity measurement.
- Focus on hyperactivity, attention span, and anxiety-related behaviors.
Main Results:
- Hypothyroid (HT) rats exhibited increased locomotion and reduced grooming in the open field test, suggesting hyperactivity and lower anxiety.
- HT rats showed impaired performance in passive and active avoidance tests, indicating deficits in learning and memory.
- HT rats displayed restlessness, shortened attention spans, and increased panic responses, consistent with ADHD-like symptoms.
Conclusions:
- Transient perinatal hypothyroidism in rats leads to significant behavioral abnormalities.
- These abnormalities, including hyperactivity and attention deficits, resemble characteristics observed in human ADHD.
- Thyroid hormone's role in CNS development is critical for normal behavioral outcomes.
Abstract:
Thyroid hormone is essential for the proper development of the mammalian central nervous system (CNS). In the present study, we examined behavioural alterations caused by transient perinatal hypothyroidism induced by an anti-thyroid drug, propylthiouracil (PTU). This drug produces perinatal disruption of the thyroid system and subsequent behavioural changes, which we investigated using a series of behavioural tests and focusing particularly on attention-deficit/hyperactivity disorder (ADHD)-like behaviours. In the open field test, both male and female rats that had experienced perinatal hypothyroidism (HT rats) showed an increased percent of locomotion behaviour and reduced grooming behaviour, suggesting that HT rats may be hyperactive and show fewer anxiety characteristics. Neither male nor female HT rats showed retention in the passive avoidance test. Male HT rats showed a significantly lower rate of correct avoidance responses than control rats in earlier sessions in the active avoidance test. In addition, we observed significant increases in the number of times that rats crossed the partition during inter-trial intervals and the percent of failure of avoidance during 5 s electrical stimuli in HT rats, suggesting that HT rats are restless, have a shortened attention span and panic easily. In measuring spontaneous motor activity during a period of darkness, male HT rats appeared to plunge into active phase with short, quick steps, while male control rats showed only long active phases during a stress-free period of darkness. These abnormal behavioural characteristics in HT rats might coincide with those found in some cases of ADHD.
