Basolateral amygdala noradrenergic influences on memory storage are mediated by an interaction between beta- and alpha1-adrenoceptors

Abstract

Extensive evidence indicates that norepinephrine modulates memory storage through an activation of beta-adrenoceptors in the basolateral nucleus of the amygdala (BLA). Recent findings suggest that the effects of beta-adrenergic activation on memory storage are influenced by alpha1-adrenoceptor stimulation. Pharmacological findings indicate that activation of postsynaptic alpha1-adrenoceptors potentiates beta-adrenoceptor-mediated activation of cAMP formation. The present study examined whether inactivation of alpha1-adrenoceptors in the BLA would alter the dose-response effects on memory storage of intra-BLA infusions of a beta-adrenoceptor agonist, as well as that of a synthetic cAMP analog. Male Sprague Dawley rats received bilateral microinfusions into the BLA of either the beta-adrenoceptor agonist clenbuterol (3-3000 pmol in 0.2 microliter) or 8-bromoadenosine 3':5'-cyclic monophosphate (8-bromo-cAMP) (0.2-7 nmol in 0.2 microliter) alone or together with the alpha1-adrenoceptor antagonist prazosin (0.2 nmol) immediately after training in an inhibitory avoidance task. Retention was tested 48 hr later. Clenbuterol induced a dose-dependent enhancement of retention, and prazosin attenuated the dose-response effects of clenbuterol. Posttraining intra-BLA infusions of 8-bromo-cAMP also induced a dose-dependent enhancement of retention latencies. However, concurrent infusion of prazosin did not alter the dose-response effects of 8-bromo-cAMP. These findings are consistent with the view that alpha1-adrenoceptors affect memory storage by modulating beta-adrenoceptor activation in the BLA. Moreover, these findings are consistent with those of pharmacological studies indicating that beta-adrenoceptors modulate memory storage by a direct coupling to adenylate cyclase, whereas alpha1-receptors act indirectly by influencing the beta-adrenoceptor-mediated influence on cAMP formation.

Fig. 1.

a, Schematic representation of the amygdaloid complex. The solid lines indicate the position of the photomicrograph (b) representing the cannula (top arrow) and the injection tip (bottom arrow) placement. L, Lateral nucleus of the amygdala.

Fig. 2.

Inhibitory avoidance retention latencies of animals that received posttraining infusion of several doses of the selective β-adrenoceptor agonist clenbuterol alone or in combination with the selective α₁-adrenoceptor antagonist prazosin into the BLA. Error bars represent mean ± SEM latency (in seconds) to enter the dark compartment on the retention test. **p < 0.01; ***p < 0.001 compared with vehicle-infused group; •••p < 0.001 compared with the corresponding groups infused with clenbuterol alone. n = 9–12 per group.

Fig. 3.

Inhibitory avoidance retention latencies of animals that received posttraining infusion of several doses of 8-bromo-cAMP, an analog of cAMP that passes the cell membrane, alone or in combination with the selective α₁-adrenoceptor antagonist prazosin into the BLA. Error bars represent mean ± SEM latency (in seconds) to enter the dark compartment on the retention test. ***p < 0.001 compared with vehicle-infused group. n = 10–13 per group.