TY - JOUR
T1 - Comparison of neuroendocrine and behavioral effects of ipsapirone, a 5-HT1A agonist, in three stress paradigms
T2 - immobilization, forced swim and conditioned fear
AU - Rittenhouse, Peter A.
AU - Bakkum, Erica A.
AU - O'Connor, Patricia A.
AU - Carnes, Molly
AU - Bethea, Cynthia L.
AU - van de Kar, Louis D.
PY - 1992/5/15
Y1 - 1992/5/15
N2 - Ipsapirone is an anxiolytic drug and a serotonin1A (5-HT1A) agonist. The aim of the present study was to investigate the effects of low doses of ipsapirone on the hormonal and behavioral response to three stress procedures: immobilization, forced swim and conditioned emotional response (CER). We examined the effect of ipsapirone (0.1, 0.5 or 1.0 mg/kg) on plasma renin concentration (PRC), adrenal corticotropic hormone (ACTH), corticosterone, prolactin and defacation in rats exposed to immobilization, forced swim or CER stress. All three stressors significantly elevated all the hormone levels (P < 0.01). Immobilization-induced elevations of PRC, and corticosterone were inhibited by the highest doses of ipsapirone (0.5 and 1 mg/kg, i.p.). However, ipsapirone did not modify the immobilization-induced elevations of plasma ACTH, prolactin or defecation. Ipsapirone was relatively ineffective at reducing the endocrine responses to forced swim. Ipsapirone reduced some, but not all of the hormonal responses to CER stress. CER-induced elevations of corticosterone and prolactin were not inhibited by ipsapirone. However, the ACTH response to CER was significantly (P < 0.01) inhibited by all doses of ipsapirone and the highest dose of ipsapirone attenuated the renin response. In contrast with the hormonal responses, ipsapirone inhibited all of the behavioral responses to CER stress. Ipsapirone inhibited CER-induced freezing behavior and defecation, while dose-dependently reversing the suppressive effect of CER on exploring, grooming and rearing behaviors. In conclusion, there is a dissociation between the influence of ipsapirone on the endocrine and behavioral responses to CER stress. Ipsapirone also has differential effects on the neuroendocrine response to the three stressors studied. Ipsapirone was most effective in attenuating the hormonal responses to CER, followed by immobilization and swim stress. Of the hormones studied, the stimulation of renin secretion after exposure to the three stressors was most sensitive to ipsapirone, while corticosterone and prolactin were the least sensitive to ipsapirone.
AB - Ipsapirone is an anxiolytic drug and a serotonin1A (5-HT1A) agonist. The aim of the present study was to investigate the effects of low doses of ipsapirone on the hormonal and behavioral response to three stress procedures: immobilization, forced swim and conditioned emotional response (CER). We examined the effect of ipsapirone (0.1, 0.5 or 1.0 mg/kg) on plasma renin concentration (PRC), adrenal corticotropic hormone (ACTH), corticosterone, prolactin and defacation in rats exposed to immobilization, forced swim or CER stress. All three stressors significantly elevated all the hormone levels (P < 0.01). Immobilization-induced elevations of PRC, and corticosterone were inhibited by the highest doses of ipsapirone (0.5 and 1 mg/kg, i.p.). However, ipsapirone did not modify the immobilization-induced elevations of plasma ACTH, prolactin or defecation. Ipsapirone was relatively ineffective at reducing the endocrine responses to forced swim. Ipsapirone reduced some, but not all of the hormonal responses to CER stress. CER-induced elevations of corticosterone and prolactin were not inhibited by ipsapirone. However, the ACTH response to CER was significantly (P < 0.01) inhibited by all doses of ipsapirone and the highest dose of ipsapirone attenuated the renin response. In contrast with the hormonal responses, ipsapirone inhibited all of the behavioral responses to CER stress. Ipsapirone inhibited CER-induced freezing behavior and defecation, while dose-dependently reversing the suppressive effect of CER on exploring, grooming and rearing behaviors. In conclusion, there is a dissociation between the influence of ipsapirone on the endocrine and behavioral responses to CER stress. Ipsapirone also has differential effects on the neuroendocrine response to the three stressors studied. Ipsapirone was most effective in attenuating the hormonal responses to CER, followed by immobilization and swim stress. Of the hormones studied, the stimulation of renin secretion after exposure to the three stressors was most sensitive to ipsapirone, while corticosterone and prolactin were the least sensitive to ipsapirone.
KW - Adrenal corticotropic hormone
KW - Corticosterone
KW - Ipsapirone
KW - Prolactin
KW - Renin
KW - Serotonin
KW - Stress
UR - http://www.scopus.com/inward/record.url?scp=0026741413&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0026741413&partnerID=8YFLogxK
U2 - 10.1016/0006-8993(92)90946-7
DO - 10.1016/0006-8993(92)90946-7
M3 - Article
C2 - 1354556
AN - SCOPUS:0026741413
SN - 0006-8993
VL - 580
SP - 205
EP - 214
JO - Brain research
JF - Brain research
IS - 1-2
ER -