DOPAMINE SENSITIVITY IN RATS SELECTIVELY BRED FOR INCREASES IN CHOLINERGIC FUNCTION

Because of the extensive literature demonstrating an interaction between cholinergic and dopaminergic systems, the Flinders Sensitive (FSL) and Flinders Resistant (FRL) Lines of rats, selectively bred for differences in cholinergic function, were tested for differences in dopamine sensitivity. Large differences in sensitivity to dopamine agonists were detected, but the direction depended upon the function: The FSL rats were supersensitive to the hypothermic effects of dopamine agonists, but were subsensitive to the stereotyping-inducing effects. Measurement of dopamine receptors by either standard binding techniques or autoradiography failed to demonstrate any receptor differences in the FSL and FRL rats. Behavioural studies with dopamine antagonists were less clear-cut, but suggested that the FSL rats might be more sensitive to their catalepsy-inducing effects. These findings indicate that the changes in dopamine sensitivity which accompany cholinergic supersensitivity are function-dependent, but are not associated with parallel changes in dopamine receptor concentration.