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Effect of methimazole-induced hypothyroidism on multiple opioid receptors in rat brain regions
H N Bhargava1, P Ramarao, A Gulati
1Department of Pharmacodynamics, University of Illinois, Chicago.
Abstract:
The effect of chronic administration of methimazole (0.05% w/v) in drinking water for 32 days to male Sprague-Dawley rats on the binding of opioid ligands, 3H-Tyr-D-Ala-Gly-MePhe-Gly-ol (DAGO, mu-receptors), 3H-Tyr-D-Ser-Gly-Phe-Leu-Thr (DSTLE, delta-receptors) and 3H-ethylketocyclazocine (EKC, kappa-receptors) to membranes of brain regions was determined. Chronic administration of methimazole to rats decreased their rate of body weight gain, colonic temperature, systolic blood pressure and heart rate in comparison to vehicle-treated rats. Administration of methimazole also decreased the serum concentration of triiodothyronine (total T3) and T4 when compared to vehicle-treated rats. The binding of 3H-DAGO to membranes of amygdala, pons and medulla, striatum, midbrain and cortex of methimazole-treated rats was greater than vehicle-treated rats, however, the binding to membranes of hypothalamus in the two treatment groups did not differ. The binding of 3H-DSTLE in amygdala and hypothalamus of methimazole-treated rats did not differ but it was significantly greater in pons and medulla, midbrain, cortex and striatum of methimazole-treated rats than vehicle-treated rats. The binding of 3H-EKC to membranes of pons and medulla was lower and of striatum and cortex of methimazole-treated rats was significantly greater than vehicle-treated rats, but the binding to membranes of amygdala, hypothalamus, and midbrain of the two treatment groups did not differ. The results indicate that brain, mu-, delta- and kappa-opioid receptors are differentially altered in hypothyroidism.
Insights
Methimazole-induced hypothyroidism in rats altered opioid receptor binding in the brain. This study reveals differential changes in mu-, delta-, and kappa-opioid receptors, indicating a link between thyroid status and brain opioid systems.
Area of Science:
- Neuroscience
- Endocrinology
- Pharmacology
Background:
- Methimazole is an antithyroid drug that induces hypothyroidism.
- Opioid receptors (mu, delta, kappa) are crucial in regulating various physiological processes.
- Thyroid hormones influence central nervous system function, including neurotransmitter systems.
Purpose of the Study:
- To investigate the impact of chronic methimazole administration on opioid receptor binding in specific brain regions of male Sprague-Dawley rats.
- To determine if experimentally induced hypothyroidism alters the binding affinity or density of mu-, delta-, and kappa-opioid receptors.
Main Methods:
- Male Sprague-Dawley rats were administered methimazole (0.05% w/v) in drinking water for 32 days.
- Physiological parameters (body weight, temperature, blood pressure, heart rate) and serum thyroid hormone levels (T3, T4) were measured.
- Radioligand binding assays were performed using [3H]DAGO (mu), [3H]DSTLE (delta), and [3H]EKC (kappa) on membranes from various brain regions.
Main Results:
- Methimazole treatment led to decreased body weight gain, colonic temperature, systolic blood pressure, and heart rate.
- Serum concentrations of total T3 and T4 were significantly reduced in methimazole-treated rats, confirming hypothyroidism.
- Opioid receptor binding showed differential changes: mu-receptor binding increased in amygdala, pons/medulla, striatum, midbrain, and cortex; delta-receptor binding increased in pons/medulla, midbrain, cortex, and striatum; kappa-receptor binding decreased in pons/medulla and increased in striatum and cortex.
- Hypothalamic binding for all receptor types and amygdala/midbrain binding for kappa-receptors remained unchanged.
Conclusions:
- Chronic methimazole-induced hypothyroidism differentially alters the binding of mu-, delta-, and kappa-opioid receptors in various rat brain regions.
- These findings suggest a significant interaction between thyroid hormone status and the central opioid system.
- The study highlights the complex neurobiological adaptations occurring in response to hypothyroidism.