The nucleus accumbens (NAcc) function is related to locomotor activity, while the lateral septal nucleus (LSN) is related to the motivational aspects of behavior. Thus, a dopaminergic lesion of the NAcc blocks the antiimmobility effect of desipramine (DMI) and this tricyclic increases the firing rate of the LSN; however, it is unknown whether a relation exists between a dopaminergic lesion of the NAcc and the response of LSN neurons to DMI treatment. Therefore, we conducted a longitudinal study to further explore the participation of NAcc dopaminergic terminals in the immobility reduction exerted by DMI in the forced swim test and its relation to the firing rate of the LSN, at the same time exploring motor and motivational aspects of DMI-dopaminergic relationships in the animals. A dopaminergic lesion was bilaterally produced by 6-hydroxydopamine (6-OHDA) injection into the NAcc of adult ovariectomized Wistar rats pretreated with DMI (25 mg/kg ip, 30 min before lesion to protect NA terminals but to destroy DA endings). Treatments with DMI or saline began 24 h after stereotaxic surgery. The results showed that DMI once a day during 9 days (10 mg/kg) reduced immobility in the forced swim test in the sham-lesion group (P<.02); however, in the dopaminergic lesion group submitted to DMI treatment, immobility remained at control level in agreement with other reports. DMI increased the firing rate of the LSN (P<.001) independently of the 6-OHDA lesion. In conclusion, the dopaminergic terminals of the NAcc seem to be essential for the motor manifestation associated with motivation induced by DMI in the forced swim test, given that the antiimmobility actions of DMI are blocked after a dopaminergic NAcc lesion; however, the effect on the firing rate of LSN neurons is still present.