title: Dissociation of analgesic and hormonal responses to forced swim stress using opioid receptor knockout mice.
abstract: Exposure to stress triggers hormonal and behavioral responses. It has been shown that the endogenous opioid system plays a role in some physiological reactions to stress. The opioid system was described to mediate analgesia induced by mild stressors and to modulate the activation of the hypothalamic-pituitary-adrenal axis. Our study assessed the contribution of opioid receptors in stress-induced analgesia and adrenocorticotropic hormone (ACTH) and corticosterone release by a genetic approach. We performed a parallel analysis of mice deficient in mu, delta, or kappa opioid receptors, as well as of triple opioid receptor knockout mice, following exposure to a mild stress (3-min swim at 32 degrees C). In wild-type mice, stress elicited an increase in jumping latency on the hot plate, which was influenced by gender and genetic background. This analgesic response was reversed both by naloxone and by the triple mutation, and decreased in mu and delta opioid receptor knockout females. In wild-type females, stress also delayed front- and hindpaw behaviors in the hot plate test and increased tail-flick latency in the tail immersion test. Opioid receptor deletion however did not affect these stress responses. In addition, stress produced an increase in ACTH and corticosterone plasma levels. This endocrine response remained unchanged in all mutant strains. Therefore our data indicate that, under our stress conditions, the endogenous opioid system is recruited to produce some analgesia whereas it does not influence hypothalamic-pituitary-adrenal axis activity. This implies that brain circuits mediating analgesic and hormonal responses to stress can be dissociated.
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, Illkirch, France.
authors.forename: Candice
authors.initials: C
authors.lastname: Contet
authors.forename: Claire
authors.initials: C
authors.lastname: Gavériaux-Ruff
authors.forename: Audrey
authors.initials: A
authors.lastname: Matifas
authors.forename: Claudia
authors.initials: C
authors.lastname: Caradec
authors.forename: Marie-France
authors.initials: MF
authors.lastname: Champy
authors.forename: Brigitte L
authors.initials: BL
authors.lastname: Kieffer
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000698:Analgesia / Q000379:methods*; D000818:Animals; D003345:Corticosterone / Q000378:metabolism*; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010147:Pain Measurement / Q000379:methods; D011930:Reaction Time / Q000502:physiology; D011957:Receptors, Opioid / Q000172:deficiency* / Q000378:metabolism*; D013312:Stress, Physiological / Q000378:metabolism* / Q000523:psychology; D013550:Swimming / Q000523:psychology
chemical_list: D011957:Receptors, Opioid; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone