Peripheral anxiogenic drug injections differentially affect cognitive and habit memory: role of basolateral amygdala

Abstract Findings from single-solution plus-maze tasks that require the use of either place or response learning indicate that post-training intra-basolateral amygdala (BLA) administration of the anxiogenic α-2 adrenoreceptor antagonist RS 79948 can both enhance dorsal striatal-dependent response learning and impair hippocampus-dependent place learning. Whether post-training peripheral administration of RS 79948 can also enhance and impair response and place learning respectively, is not known. If peripheral drug administration can also produce this “dual” effect on cognitive and habit memory, it would be of interest to know whether the functional integrity of the BLA is critical. In order to examine these questions, the present experiments combined peripheral administration of RS 79948 with concurrent neural inactivation of the BLA. Adult male Long–Evans rats were trained in place or response learning tasks in a water plus-maze. On days 1–3 of training, rats received post-training peripheral injections of saline or RS 79948 (0.1 mg/kg) combined with intra-BLA injections of saline or the sodium channel blocker bupivacaine (1.0% solution, 0.5 μl). Post-training peripheral injections of RS 79948 enhanced acquisition of response learning, and impaired acquisition of place learning. Bupivacaine infusions into the BLA had no effect on acquisition of either task. However, intra-BLA infusions of bupivacaine blocked both the enhancement of response learning and the impairment of place learning produced by RS 79948. Taken together, the findings indicate that although the functional integrity of BLA is not necessary for acquisition of place and response learning, BLA activity is critical in order for peripheral injections of an anxiogenic drug to differentially modulate hippocampus-dependent and dorsal striatal-dependent memory.