Relationship of increased food intake and plasma ACTH levels to 5-HT1A receptor activation in rats.
Various putative agonists of the 5-HT1A receptor subtype induce feeding in rats, probably by activating raphé somatodendritic 5-HT autoreceptors. These drugs also produce a marked increase in plasma concentrations of corticotropin (ACTH). In the present experiment we attempted to localize the site of action of 5-HT1A agonists on the secretion of ACTH and examined the relationship between 5-HT1A agonist-induced feeding and ACTH secretion. Rats were injected with either the high affinity 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) (0.016-1.0 mg/kg, s.c.) or the novel anxiolytics buspirone, gepirone or ipsapirone (2.0-16.0 mg/kg, s.c.), and either had their food intake measured 2 hr post injection or were sacrificed 30-40 min post injection for measurement of plasma ACTH. Plasma ACTH also was measured in rats pretreated with the serotonin synthesis inhibitor, para-chlorophenylalanine (PCPA) for three days (150 mg/kg, i.p. per day) and subsequently injected with 8-OH-DPAT (0.3 mg/kg, s.c.). As previously reported, the 5-HT1A agonists increased both food agonists increased both food intake and plasma ACTH concentrations. After 8-OH-DPAT, ipsapirone and gepirone the amount of food consumed was positively correlated with the concentration of plasma ACTH. No such correlation was evident following buspirone. PCPA pretreatment resulted in near total depletion of brain 5-HT content but had no effect on the ACTH rise induced by 8-OH-DPAT. Therefore, in contrast to the presynaptic site previously proposed for 5-HT1A agonist-induced feeding, the present results suggest a agonist-induced feeding, the present results suggest a postsynaptic location for the 5-HT1A receptor mediating ACTH release.
Gilbert
F
F
Merck Sharp & Dohme Research Laboratories, Neuroscience Research Center, Harlow, Essex, England.
Dourish
C T
CT
Brazell
C
C
McClue
S
S
Stahl
S M
SM
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000324:Adrenocorticotropic Hormone / Q000097:blood*; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001835:Body Weight; D001921:Brain / Q000187:drug effects*; D002065:Buspirone / Q000494:pharmacology; D004435:Eating / Q000187:drug effects*; D008297:Male; D009281:Naphthalenes / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D011985:Receptors, Serotonin / Q000187:drug effects*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*
D014151:Anti-Anxiety Agents; D009281:Naphthalenes; D011743:Pyrimidines; D011985:Receptors, Serotonin; D013764:Tetrahydronaphthalenes; C043077:ipsapirone; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000324:Adrenocorticotropic Hormone; C039979:gepirone; D002065:Buspirone