Selective activation of mesoamygdaloid dopamine neurons by conditioned stress: attenuation by diazepam.
Populations of dopamine (DA) neurons in the rat brain are selectively activated by stress, and the response is attenuated by the administration of anxiolytics. Given the role of the component nuclei of the amygdaloid complex in conditioned associations, stress responses and the anxiolytic effects of benzodiazepines, we hypothesized that particular mesoamygdaloid DA projections might be especially sensitive to the effects of conditioned stress and to diazepam (DZ). We mapped the effect of a conditioned stressor on the concentration of the DA metabolite homovanillic acid (HVA) in distinct amygdaloid nuclei and other brain nuclei and areas and the effect of DZ (1 or 3 mg/kg) on the conditioned response in drug-experienced subjects. The conditioned stress paradigm resulted in significant elevations in classical indices of stress, including serum corticosterone and plasma epinephrine. Conditioned stress-induced increases in the estimated activity of DA neurons were specific for DA neurons projecting to the central, basolateral and lateral amygdaloid nuclei, and for DA projections to the dorsal septal nucleus. Conditioned stress-induced increases in the HVA concentration of responsive amygdaloid nuclei were antagonized by low, anxiolytic doses of DZ. These results indicate a role for a subset of mesoamygdaloid DA projections in transducing the impact of perceived stressors on the output of the amygdaloid complex. A role for particular amygdaloid DA projections in the formation of conditioned fear or anticipatory anxiety and its modulation by anxiolytics is also suggested.
Coco
M L
ML
Department of Pharmacology, Duke University Medical Center, Durham, NC 27710.
Kuhn
C M
CM
Ely
T D
TD
Kilts
C D
CD
D000679:Amygdala / Q000737:chemistry / Q000187:drug effects* / Q000503:physiopathology; D000818:Animals; D001007:Anxiety / Q000503:physiopathology; D002851:Chromatography, High Pressure Liquid; D003214:Conditioning, Classical; D003345:Corticosterone / Q000097:blood; D003975:Diazepam / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D006719:Homovanillic Acid / Q000032:analysis; D008297:Male; D009474:Neurons / Q000187:drug effects*; D011388:Prolactin / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D013312:Stress, Physiological / Q000378:metabolism / Q000503:physiopathology*
D011388:Prolactin; D003975:Diazepam; D004298:Dopamine; D003345:Corticosterone; D006719:Homovanillic Acid