title: Central oxytocin receptor stimulation attenuates the orexigenic effects of butorphanol tartrate.
abstract: Butorphanol tartrate (BT), a mixed µ/κ/δ opioid receptor agonist, is one of the most potent orexigens known to date. The central mechanisms through which BT causes hyperphagia are largely unknown. Interestingly, BT suppresses meal-end activation of neurons synthesizing anorexigenic neuropeptide, oxytocin (OT), which suggests that BT promotes hyperphagia by silencing OT-derived satiety signaling. As OT terminates consumption by acting by distinct hindbrain and forebrain circuits, we investigated whether stimulation of the OT receptor in the forebrain or the hindbrain [through lateral ventricular (LV) and fourth ventricular (4V) OT injections] leads to termination of food intake induced by BT. We established effective doses of BT on chow intake in ad-libitum-fed and overnight-deprived rats as well as effective doses of LV and 4V OT in deprived animals. Then, we determined doses of LV and 4V OT that reduce hyperphagia produced by BT in sated and deprived rats. Finally, we assessed whether OT's effects on BT-induced feeding can be suppressed by an OT receptor antagonist. 4 mg/kg BT increased intake in ad-libitum-fed and overnight-deprived rats, whereas LV and 4V OT at 1 μg caused a decrease in deprived rats. BT-induced chow intake in hungry and sated animals was suppressed by a very low, 0.1 μg dose of 4V OT, whereas 1 μg OT was effective LV. The effect of OT was attenuated by OT receptor antagonist, L-368 899. Reduced activity of the OT circuit, especially its hindbrain component, is a critical factor in shaping the magnitude of consumption in response to BT treatment.
authors.affiliation: aDepartment of Food Science and Nutrition, University of Minnesota, St Paul, Minnesota, USA bDepartment of Biological Sciences, University of Waikato, Hamilton, New Zealand.
authors.forename: Pawel K
authors.initials: PK
authors.lastname: Olszewski
authors.forename: Oscar A
authors.initials: OA
authors.lastname: Klockars
authors.forename: Anica
authors.initials: A
authors.lastname: Klockars
authors.forename: Allen S
authors.initials: AS
authors.lastname: Levine
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002077:Butorphanol / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D004435:Eating / Q000187:drug effects; D005215:Fasting / Q000502:physiology; D006963:Hyperphagia / Q000139:chemically induced* / Q000188:drug therapy*; D008297:Male; D009294:Narcotics / Q000494:pharmacology*; D010121:Oxytocin / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018045:Receptors, Oxytocin / Q000378:metabolism*; D013997:Time Factors
chemical_list: D009294:Narcotics; D018045:Receptors, Oxytocin; D010121:Oxytocin; D002077:Butorphanol