The significance of?-adrenoceptor down regulation in the desipramine action in the forced swimming test

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Abstract
The present studies were undertaken to clarify whether centralβ-adrenoceptor down regulation is responsible for the greater effect of chronic treatment with desipramine (DMI) compared with acute treatment in the forced swimming test in rats. Repetitive administration of DMI activated the rat behaviour pattern and consequently reduced the duration of immobility. The degree of activation depended on the length of treatment, i.e. no effect when given in a single dose, moderate effect when given subchronically (3 doses) and marked activation after chronic (31 doses) treatment. Chronic treatment with DMI also produced a decrease in3H-dihydroalprenolol (3H-DHA) binding site in the cerebral cortex. Acute stimulation of brainβ-adrenoceptors by intracerebroventricular (i.c.v.) isoprenaline significantly, though partially, attenuated the behavioural effect of chronic DMI by β1-adrenoceptor-related mechanisms. Similarly, chronic i.c.v. co-administration of atenolol or practolol, β1-adrenoceptor antagonists, together with DMI attenuated bothβ-adrenoceptor down regulation and the behavioural activation by chronic DMI. On the other hand, chronic i.c.v administration of isoprenaline, supposedly leading to down regulation ofβ-adrenoceptors, facilitated the activating behavioural effect of DMI, as a single dose became effective. Changes, however, in3H-DHA binding parameters in the cerebral cortex were not observed after chronic isoprenaline. These results suggest that down regulation ofβ-adrenoceptors in brain is reponsible, at least in part, for the marked activatory effect of chronic DMI in the forced swimming test, possibly by reducing an inhibitory function of β1-adrenoceptor mediated mechanisms.