Noradrenergic agonist administration into the central nucleus of the amygdala increases the tail-flick latency in lightly anesthetized rats

Abstract

The amygdala is a medial forebrain structure with an established role in nociceptive modulation, including the expression of stress-induced hypoalgesia (SIH). Projections from the locus coeruleus increase levels of noradrenaline in the amygdala during acute stress. alpha(2)-Noradrenergic receptor agonists have significant clinical utility as analgesic agents. We therefore hypothesized that alpha(2)-noradrenergic activation of the amygdala may result in behaviorally measurable hypoalgesia. Lightly anesthetized rats underwent microinjection of the alpha(2)-noradrenergic agonist clonidine into the amygdala and intermittent measurement of thermal nociception using the tail-flick latency (TFL). Bilateral microinjection of clonidine into the central nucleus of the amygdala (CeA) resulted in a significant, dose-dependent increase in TFL. This effect was blocked by systemic pre-treatment with the alpha(2)-antagonist yohimbine or by local pre-injection of the alpha(2)-antagonist idazoxan but not by local pre-injection of the alpha(1)-antagonist WB-4101. When injected alone, no antagonist resulted in a significant change in TFL compared with baseline. Clonidine injection into the amygdala but outside the CeA, including the basolateral nucleus of the amygdala, did not significantly alter TFL. These results demonstrate that anatomically and pharmacologically specific activation of alpha(2)-receptors in the CeA in lightly anesthetized rats results in behaviorally measurable antinociception.

Cognitive Impairment in Pain through Amygdala-Driven Prefrontal Cortical Deactivation

“…This first set of data is consistent with a serial model that involves BLA to CeA projections to execute appropriate emotional responses (Sah et al, 2003;Maren and Quirk, 2004;Phelps and Ledoux, 2005;Seymour and Dolan, 2008;Ehrlich et al, 2009). The result is novel and important because pain-related functional changes in the BLA were not known and previous evidence suggested potentially different roles of BLA and CeA in pain modulation (Manning and Mayer, 1995;Tanimoto et al, 2003;Carrasquillo and Gereau, 2007;Ortiz et al, 2007) and in certain aspects of emotion-related behaviors (Seymour and Dolan, 2008;Roozendaal et al, 2009). …”

Lateral Paracapsular GABAergic Synapses in the Basolateral Amygdala Contribute to the Anxiolytic Effects of β3 Adrenoceptor Activation

“…BRL or saline was injected as described above and the behavioral tests were administered 5 min after injections. Because BRL had not previously been used in microinjection studies, the dose selected was based on an extensive comparison of the effective concentration ranges of NE and other AR agonists used in slice electrophysiological and in vivo microinjection studies (NE: Berlau and McGaugh, 2006; Liu et al , 2006; clonidine ( α 2-AR agonist): Ortiz et al , 2007; Stevens et al , 2004; isoproterenol ( β -AR agonist): Egli et al , 2005; Selvage and Rivier, 2003). After completion of the behavioral testing phase of the experiment, all subjects were given a lethal dose of sodium pentobarbital and, once deeply anesthetized, were transcardially perfused with buffered saline, followed by 10% formalin in saline.…”

Effect of Glucocorticoid Receptor Blockade on Analgesic Effect of Corticotropin-Releasing Factor

“…Nembutal in a dose of 40 mg/kg was injected intraperitoneally 20 min before studying the baseline level of pain sensitivity [1][2][3]12]. The pain threshold or latency of the nociceptive reaction in anesthetized rats was measured 3, 8, 15, 20, and 30 min after CRF injection.…”