title: Behavioral, central monoaminergic and hypothalamo-pituitary-adrenal axis correlates of fear-conditioned analgesia in rats.
abstract: Fear-conditioned analgesia is an important survival response which is expressed upon re-exposure to a context previously paired with a noxious stimulus. The aim of the present study was to characterize further the behavioral, monoaminergic and hypothalamo-pituitary-adrenal axis alterations associated with expression of fear-conditioned analgesia. Rats which had received footshock conditioning 24 h earlier, exhibited reduced formalin-evoked nociceptive behavior upon re-exposure to the footshock chamber, compared with non-footshocked formalin-treated rats. Intra-plantar injection of formalin reduced the duration of contextually-induced freezing and 20-40 kHz ultrasound emission. Intra-plantar injection of formalin to non-footshocked, non-conditioned rats did not induce ultrasonic vocalizations. Intra-plantar injection of formalin to footshock-conditioned rats, significantly increased tissue levels of 3,4-dihydroxyphenylacetic acid and the 3,4-dihydroxyphenylacetic acid:dopamine ratio in the periaqueductal gray and reduced levels of dopamine in the thalamus, compared with saline-treated footshocked controls. Non-footshocked, non-conditioned rats were capable of mounting a robust formalin-evoked increase in plasma corticosterone levels. Moreover, plasma corticosterone levels were significantly higher in saline-treated, footshock conditioned rats compared with saline-treated non-footshocked rats and levels did not differ between saline- and formalin-treated footshock conditioned rats. Assessment of the effects of the intra-plantar injection procedure revealed an attenuation of short-term extinction of contextually-induced freezing in rats anesthetized for intra-plantar injection of saline compared with non-anesthetized, non-injected rats as well as discrete effects on monoamines, their metabolites and plasma corticosterone levels. These data extend behavioral characterization of the phenomenon of fear-conditioned analgesia and suggest that measurement of ultrasound emission may be used as an ethologically relevant index of the defense response during fear-conditioned analgesia. Ultrasonic vocalization may also be a useful behavioral output to aid separation of nociception and aversion. The data provide evidence for discrete alterations in dopaminergic activity in the periaqueductal gray and thalamus and for altered hypothalamo-pituitary-adrenal axis activity following expression of defensive behavior.
authors.affiliation: Institute of Neuroscience, School of Biomedical Sciences, University of Nottingham, Queen's Medical Centre, Nottingham NG7 2UH, UK. David.Finn@Nuigalway.ie
authors.forename: D P
authors.initials: DP
authors.lastname: Finn
authors.forename: M D
authors.initials: MD
authors.lastname: Jhaveri
authors.forename: S R G
authors.initials: SR
authors.lastname: Beckett
authors.forename: A
authors.initials: A
authors.lastname: Madjd
authors.forename: D A
authors.initials: DA
authors.lastname: Kendall
authors.forename: C A
authors.initials: CA
authors.lastname: Marsden
authors.forename: V
authors.initials: V
authors.lastname: Chapman
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000698:Analgesia; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D015306:Biogenic Monoamines / Q000378:metabolism*; D001921:Brain / Q000378:metabolism; D003213:Conditioning, Psychological; D003345:Corticosterone / Q000097:blood; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D004558:Electric Stimulation / Q000009:adverse effects; D005239:Fear / Q000502:physiology*; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism*; D008297:Male; D009434:Neural Pathways / Q000378:metabolism; D010146:Pain / Q000378:metabolism* / Q000503:physiopathology; D010147:Pain Measurement / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology*; D010913:Pituitary-Adrenal System / Q000378:metabolism*; D051381:Rats; D013315:Stress, Psychological / Q000378:metabolism / Q000503:physiopathology; D014828:Vocalization, Animal / Q000187:drug effects / Q000502:physiology
chemical_list: D015306:Biogenic Monoamines; D015102:3,4-Dihydroxyphenylacetic Acid; D004298:Dopamine; D003345:Corticosterone