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Evidence for post-synaptic changes mediating increased behavioural sensitivity to dopamine receptor agonists in
1Department of Clinical Pharmacology, Flinders University of South Australia, Bedford Park.
Progress in Neuro-Psychopharmacology & Biological Psychiatry
|January 1, 1988
Summary
Hypothyroidism in male rats altered behavioral responses to dopamine agonists and antagonists. These changes may stem from altered post-synaptic events, not receptor density.
Area of Science:
- Neuroscience
- Endocrinology
- Pharmacology
Background:
- Hypothyroidism is a condition characterized by an underactive thyroid gland.
- Thyroid hormones play a crucial role in brain development and function.
- Dopamine receptors are implicated in various behavioral processes.
Purpose of the Study:
- To investigate the effects of hypothyroidism on dopamine receptor-mediated behaviors in male rats.
- To explore the relationship between thyroid status and dopamine receptor sensitivity.
Main Methods:
- Hypothyroidism was induced in male rats using propylthiouracil (PTU).
- Behavioral responses to various dopamine receptor agonists and antagonists were assessed.
- Ligand binding studies were performed on striatal tissue.
- Dopamine-stimulated cyclic AMP (cAMP) levels were measured.
Main Results:
- Hypothyroid rats exhibited heightened behavioral responses to D1 and D2 dopamine receptor agonists.
- Responses to D1 and D2 antagonists differed, with decreased sensitivity to SCH 23390 and increased sensitivity to haloperidol.
- No significant changes in D1 or D2 receptor binding affinity or concentration were observed.
- Hypothyroid rats showed a greater increase in dopamine-stimulated cAMP in the striatum.
Conclusions:
- Altered behavioral sensitivity to dopaminergic agents in hypothyroidism is not due to changes in receptor number or affinity.
- Post-synaptic alterations, specifically in dopamine-stimulated cAMP signaling, likely underlie the observed behavioral changes.