TitleEffects of acute microinjections of thyroid hormone to the median preoptic nucleus of hypothyroid adult male rats on sleep, motor activity, and body temperature
NameMoffett, Steven (author), Morgan, Mark D (chair), Martin, Joseph V (internal member), Saidel, William M (internal member), McIlroy, Patrick J (internal member), Camden Graduate School, Camden Graduate School,
Thyroid hormones--Physiological effect,
Rats as laboratory animals
DescriptionThyroid hormone's role as a genomic regulator of basal metabolic rate does not explain neurological changes in patients with dysthyroidism. Hypothyroidism, characterized by depressive symptoms including somnolence, intellectual deterioration, and coma, and hyperthyroidism, illustrated by symptoms including insomnia, anxiety, and seizures, imply a mechanism of thyroid hormone action which influences behavior. In adults, thyroid hormone is taken up to discrete brain areas by organic anion and monocarboxylate transport proteins. One site of distribution, the median preoptic nucleus (MePO), contains clusters of sleep-active neurons and is considered a key sleep-regulatory structure. To test the acute effect of thyroid hormone at this locus, we stereotaxically implanted adult hypothyroid rats with microinjection guide cannulae at the MePO and installed electrodes and miniature transmitters for recording EEG, EMG, core body temperature, and locomotor activity. The rats were rendered hypothyroid by administration of 0.02% 6-n-propyl-2-thiouracil in drinking water until body weight plateaued, indicating a hypothyroid condition. Rats were given a series of dosages (0.3 μg, 1 μg, 3 μg, or 10 μg in 0.25μL vehicle) of L-3,3´,5-triiodothyronine (T3) in four weekly 48-hour tests. Each week, rats were bilaterally microinjected with a control solution. After 24 hours of recording, each rat was microinjected with one of the above doses of T3 and recorded for an additional 24 hours. In seven rats with histologically-confirmed cannulae placements in the MePO, we observed significant effects on REM, non-REM, total sleep, core body temperature and motor activity analyzed by 2-way ANOVAs. For each sleep parameter the effect of dose of hormone was significant (p < 0.0001), as was the effect of time after injection (p<0.0001), except for in REM sleep. Temperature and activity also showed significant effects of dose (p < 0.02) and time (p < 0.001). There was no significant interaction between dose and time factors in any ANOVA. Since the effects of T3 were seen within hours of acute injection, the data are most consistent with a non-genomic mechanism of action of thyroid hormones in the adult brain. The mechanism of thyroid hormone action may be due to inhibition of the GABAA receptor, by an unknown protein phosphorylation effect, or by its actions as an adrenergic system analogue.
NoteIncludes bibliographical references
Noteby Steven Moffett
CollectionCamden Graduate School Electronic Theses and Dissertations
Organization NameRutgers, The State University of New Jersey
RightsThe author owns the copyright to this work.