Intermittent
subcutaneous injection of
teriparatide, an active fragment of human
parathyroid hormone, is clinically used for the treatment of
osteoporosis. Patients suffer from
nausea, which is one of the side effects
teriparatide induces; however, the etiology of
teriparatide-induced
nausea remains unknown. We have reported
pica,
kaolin ingestion behavior, can be used as an assessment of
nausea-related response in rats. In this study, we investigated the characteristics of
teriparatide-induced
pica and the abilities of
anti-emetic drugs to inhibit
teriparatide-induced
pica. Male and female adolescent (4-week-old), young (8-week-old), and adult (30-week-old) naive rats, and ovariectomized (OVX: 17-week-old) and
sham-operated (17-week-old) rats subcutaneously received
teriparatide (0.4 mg/kg, n=4), and their
kaolin and food intakes were monitored for 24 h after the injection. Among the tested rats, we found that OVX rats, rather than male, female, and
sham-operated rats, showed marked
teriparatide-induced
pica (0 mg/kg: 0.17±0.07 g, 0.4 mg/kg: 6.18±0.91 g).
Teriparatide-induced
pica in OVX rats was inhibited by intraperitoneal pretreatment with
serotonin 5-HT3 (
granisetron 0.5 mg/kg),
dopamine D2 (
prochlorperazine 0.5 mg/kg), neurokinin NK1 (
fosaprepitant 1 mg/kg), and
histamine H1 (
diphenhydramine 10 mg/kg) receptor antagonists to 70%, 11%, 19%, and 59% of that in vehicle-treated control, respectively. These results suggest that
teriparatide-induced
pica in OVX rats has the potential to reflect
teriparatide-induced
nausea; 5-HT3, D2, NK1, and
H1 receptor activation is involved in the development of this behavior; antagonists of these receptors have the potential to be medical candidates used as treatments for
teriparatide-induced
nausea in human patients.