Does amygdaloid corticotropin-releasing hormone (CRH) mediate anxiety-like behaviors? Dissociation of anxiogenic effects and CRH release.
The brain corticotropin-releasing hormone (CRH) circuits are activated by stressful stimuli, contributing to behavioral and emotional responses. The present study assessed anxiety-like responses and in vivo neurochemical alterations at the central nucleus of the amygdala (CeA) evoked by exposure to an unfamiliar (anxiogenic) environment. Also, the impact of anxiolytic treatments and those that affect CRH were assessed in this paradigm. Novel environment (new cage) markedly suppressed ingestion of a palatable snack. This effect was dose-dependently antagonized by diazepam and was utilized as an index of anxiety in the rodent. Although exposure to a novel environment also stimulated the in vivo release of CRH and glutamate at the CeA, various CRH antagonists (e.g. alphah-CRH, Calpha-MeCRH, CP-154,526, antisauvagine-30, preproTRH178-199) did not attenuate the stressor-elicited behavioral suppression, although Calpha-MeCRH was found to attenuate the freezing response elicited by contextual stimuli that were associated with previously administered footshock. Moreover, central infusion of CRH failed to suppress snack consumption in the home cage. Although diazepam had potent anxiolytic effects in this paradigm, this treatment did not prevent the stressor-associated release of CRH and glutamate at the CeA. Thus, while neural circuits involving CRH and/or glutamatergic receptors at the CeA may be activated by an unfamiliar environment, the data challenge the view that activation of these receptors is necessary for the expression of anxiety-like behavioral responses. Rather than provoking anxiety, these systems might serve to draw attention to events or cues of biological significance, including those posing a threat to survival.
Merali
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Institute of Mental Health Research, University of Ottawa, Ottawa, Ontario, Canada K1N 6 N5. merali@uottawa.ca
Khan
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Michaud
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Shippy
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Anisman
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D000679:Amygdala / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D014151:Anti-Anxiety Agents / Q000627:therapeutic use; D001007:Anxiety / Q000188:drug therapy / Q000378:metabolism*; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D001839:Bombesin / Q000494:pharmacology; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology*; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism* / Q000494:pharmacology / Q000502:physiology; D003975:Diazepam / Q000627:therapeutic use; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects / Q000523:psychology; D004597:Electroshock / Q000379:methods; D004777:Environment; D018698:Glutamic Acid / Q000378:metabolism; D006727:Hormone Antagonists / Q000494:pharmacology; D008297:Male; D017551:Microdialysis / Q000379:methods; D010446:Peptide Fragments / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D011863:Radioimmunoassay / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors
D014151:Anti-Anxiety Agents; C101628:CP 154526; D006727:Hormone Antagonists; D010446:Peptide Fragments; D011743:Pyrimidines; D011758:Pyrroles; D018019:Receptors, Corticotropin-Releasing Hormone; C069206:alpha helical corticotropin-releasing hormone; C116607:antisauvagine 30; D018698:Glutamic Acid; D003346:Corticotropin-Releasing Hormone; D001839:Bombesin; D003975:Diazepam