In vivo microdialysis was used to study the effect of chronic desipramine (DMI, 5 mg/kg, twice daily for 21 days) on increases in interstitial dopamine (DA) produced by local administration of d-amphetamine (1.0, 3.3 and 10.0-mu-M) in the nucleus accumbens. Locally applied amphetamine increased interstitial DA in a dose-dependent manner. The amphetamine-induced increase was significantly greater in the DMI treated animals. These data suggest that chronic DMI may directly influence the functional status of the DA terminals in the nucleus accumbens.