Chronic antidepressant administration fails to attenuate apomorphine-induced decreases in rat striatal dopamine metabolites.

The responsiveness of the rat striatal dopamine (DA) receptor system to apomorphine (APO) was assessed after 10 days of antidepressant administration. Desipramine (DMI), dothiepin (DOTH), iprindole (IPR) and nomifensine (NOM) were administered intra-peritoneally, twice daily, to rats for 10 days and 42 h after the last drug dose, animals were injected with APO (25 or 200 micrograms/kg s.c., 15 min) or vehicle. Striatal content of 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), assayed using a recently developed high-performance liquid chromatography-electrochemical detection (HPLC-ECD) method, showed that prolonged administration of all four antidepressant drugs failed to modify the effect of APO on DA metabolism. The results of these experiments therefore do not provide evidence to support the suggestion that subsensitivity in presynaptic DA 'autoreceptors' is a significant biochemical correlate of chronic antidepressant drug administration.