Noradrenergic agonist administration into the central nucleus of the amygdala increases the tail-flick latency in lightly anesthetized rats.
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.
Ortiz
J P
JP
Department of Neurological Surgery, Oregon Health & Science University, Mail code: CH8N, 3303 Southwest Bond Avenue, Portland, OR 97239, USA.
Heinricher
M M
MM
Selden
N R
NR
D000322:Adrenergic Agonists / Q000494:pharmacology*; D018674:Adrenergic Antagonists / Q000494:pharmacology; D000679:Amygdala / Q000187:drug effects / Q000378:metabolism*; D000777:Anesthetics / Q000494:pharmacology; D000818:Animals; D003000:Clonidine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions / Q000502:physiology; D008297:Male; D008845:Microinjections; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology; D009638:Norepinephrine / Q000819:agonists / Q000378:metabolism*; D010146:Pain / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D010147:Pain Measurement / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects / Q000378:metabolism*; D012018:Reflex / Q000187:drug effects / Q000502:physiology
D000322:Adrenergic Agonists; D018674:Adrenergic Antagonists; D000777:Anesthetics; D018341:Receptors, Adrenergic, alpha-2; D003000:Clonidine; D009638:Norepinephrine
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