Evidence for post-synaptic changes mediating increased behavioural sensitivity to dopamine receptor agonists in hypothyroid rats.

1. Hypothyroidism was maintained for four weeks in male rats by administration of PTU daily. 2. Hypothyroid rats showed increased behavioural responses to apomorphine, a mixed D1/D2 dopamine receptor agonist, LY 171555, a selective D2 agonist and to SKF 38393, a selective D1 agonist, compared with euthyroid controls. 3. Responses to the selective D1 antagonist, SCH 23390, were decreased, but were increased to the D2 antagonist, haloperidol, in hypothyroid rats. 4. Ligand binding studies showed no significant differences in the affinity and concentration of D1 or D2 receptor sub-types in the striatum of hypothyroid compared with euthyroid rats. 5. However, hypothyroid rats had a greater increase in dopamine stimulated cyclic AMP in the striatum than euthyroid controls. 6. It is concluded that the changes in behavioural sensitivity observed in hypothyroid rats may be associated with these alterations in post-synaptic events.