Minocycline produces antidepressant-like actions in male rats tested in the forced swimming test (FST) and synergizes with several glutamate receptor antagonists. However, the limbic regions implicated in the antidepressant-like actions of minocycline are unknown. The objective of the present study was to test the potential antidepressant activity of nucleus accumbens infusions of minocycline alone or combined with antidepressant drugs or with several glutamate receptor antagonists, using the time-sampling method in the FST. The results show that intra-NAcc infusions of minocycline reduced immobility (1.0 microg, P<0.05; 1.5 microg, P<0.05) by increasing climbing (1.0 microg, P<0.05; 1.5 microg, P<0.05) in the FST. Likewise, systemic injections of desipramine (P<0.05), fluoxetine (P<0.05) or several glutamate receptor antagonists: EMQMCM (P<0.05), MTEP (P<0.05) or dizocilpine (P<0.05) combined with intra-nucleus accumbens infusions of vehicle produced antidepressant-like actions. The subthreshold dose of intra-nucleus accumbens infusions of minocycline combined with systemic injections of subthreshold doses of desipramine (P<0.05) or EMQMCM (P<0.05) or MTEP (P<0.05) or dizocilpine (P<0.05) produced antidepressant-like actions. It is concluded that intra-NAcc infusions of minocycline alone or combined with systemic injections of desipramine or with systemic injections of several glutamate receptor antagonists produced antidepressant-like actions in the FST.