Research with dopamine D(1) receptor antagonists or neuronal inactivating agents suggests that there is dissociable regulation of cocaine-seeking behavior by the rostral and caudal basolateral amygdala. In the present study, discrete infusions of the D(1) receptor agonist SKF 81297 (0.0-0.8 microg per side) were compared with those of the D(1) receptor antagonist SCH 23390 (0.0-2.0 microg per side) to demonstrate directly the importance of D(1) receptor mechanisms within the rostral and caudal basolateral amygdala for their functional heterogeneity in regulating cocaine-seeking behavior. Under a second-order schedule, cocaine-seeking behavior was studied during maintenance (cocaine and cocaine cues present) and reinstatement (only cocaine cues present). Food-maintained responding was used to examine the specificity of maximal behaviorally effective doses of SKF 81297 and SCH 23390. The results demonstrated that the D(1) agonist (0.4 or 0.8 microg) increased and the D(1) antagonist (1.0 microg) decreased cocaine-seeking behavior during maintenance when infused into the caudal but not the rostral basolateral amygdala. Cocaine intake was not affected by the agonist, and was decreased by the antagonist. During reinstatement, the D(1) agonist (0.4 microg) increased and the D(1) antagonist (1.0 microg) decreased cocaine-seeking behavior when infused into the rostral but not the caudal basolateral amygdala. In tests for behavioral specificity, the above effective doses of SKF 81297 and SCH 23390 used in self-administration experiments did not alter food-maintained responding. However, the 2.0-microg dose of SCH 23390 suppressed drug-maintained and food-maintained responding after infusion into both subregions. Collectively, these findings indicate dissociable sensitivity to D(1) receptor ligands within the caudal and rostral basolateral amygdala for altering cocaine-seeking behavior under different conditions that model phases of addiction.