Clonidine injections into the lateral nucleus of the amygdala block acquisition and expression of fear‐potentiated startle

Abstract

Numerous studies of aversive learning with different animal models have shown that the noradrenergic system has an important role in the acquisition, consolidation and expression of aversive learning. We used intracerebral clonidine injections to investigate the role of the noradrenergic amygdaloid system in the fear-potentiated startle paradigm. Clonidine is a noradrenergic alpha2-receptor agonist which can decrease noradrenergic transmission by stimulating presynaptic alpha2-receptors. Rats received injections of 0, 2.5, 5 and 10 nmol clonidine into the lateral amygdala (i) before fear-conditioning, (ii) immediately after fear-conditioning, (iii) before testing and (iv) before both fear-conditioning and the testing of conditioned fear. Clonidine injections blocked the acquisition and expression of conditioned fear. The effect on acquisition was not caused by state-dependency or possible side-effects of clonidine on consolidation. Given that clonidine decreases amygdaloid noradrenaline release, these results show a crucial role of noradrenergic transmission within the amygdala in classical fear-conditioning. Surprisingly, both the acquisition and the expression of conditioned fear were blocked after amygdaloid injections of clonidine, suggesting that amygdaloid noradrenaline is necessary to induce both unconditioned and conditioned fear.

Norepinephrine enables the induction of associative long-term potentiation at thalamo-amygdala synapses

“…These findings, although arguing against an essential function of NE in consolidation of fear memory, do not exclude a role for NE in the mechanisms of short-term memory of auditory fear conditioning. Consistent with the notion that endogenously released NE may be required for the acquisition of fear memory, it was demonstrated earlier that pretraining manipulations of the adrenergic activity in the amygdala impair auditory fear conditioning (28). Another interesting possibility is that the NE-mediated modulation of inhibition in the BLA could also play a role in fear extinction (29).…”

Role of Norepinephrine in Modulating Inhibitory Avoidance Memory Storage: Critical Involvement of the Basolateral Amygdala

“…In addition, they fit with previous reports suggesting that the effects of peripheral administration of 2-adrenergic compounds on learning and memory performance are mediated through a direct action on central NE release [136][137][138][139] and with previous results implicating amygdala 2-adrenoceptors in footshock-based learning [140,141]. Moreover, they clearly indicate that, in addition to involvement of 1-and -adrenoceptors, 2-adrenoceptors in the BLA are involved in mediating the effects of training-induced or experimentally administered NE on memory storage [128,131].…”

Alpha2A-Adrenoceptors are Important Modulators of the Effects of D-Amphetamine on Startle Reactivity and Brain Monoamines

“…Earlier studies have shown that the a 2 -AR agonist clonidine decreases startle after systemic administration in humans (Kumari et al, 1996) and rats (Davis et al, 1977), and after spinal (Davis and Astrachan, 1981) or intra-amygdaloid (Schulz et al, 2002) administration in rats. The almost totally abolished startle reflex of WT mice after Dex 10 and especially 30 mg/kg was likely due to its sedative effect.…”