title: Effect of the mu-opioid agonist DAMGO on medial basal hypothalamic neurons in beta-endorphin knockout mice.
abstract: The endogenous opioid neurotransmitter beta-endorphin (beta-END), a product of the proopiomelanocortin (POMC) gene, is strongly implicated in the control of the female reproductive cycle, stress responses, and antinociception. Using selective gene targeting, we have generated a strain of mice that do not express any beta-END. These mice exhibit both normal reproduction and normal basal and stress-induced hypothalamic-pituitary-axis activity, but exhibit a significantly attenuated opioid-mediated stress-induced analgesia. To further understand the cellular bases of these responses, we have studied mediobasal hypothalamic (MBH) neurons, including POMC neurons, using whole-cell patch recording in an in vitro slice preparation. Twenty-seven MBH cells were recorded in wild-type and 25 MBH cells were recorded in beta-END knockout mice. Neurons from both genotypes showed a significant positive correlation between DAMGO concentration (from 30 nM to 10 microM) and the induced outward K(+) current. The genotypes did not differ, however, in either the DAMGO-induced maximum outward current response or EC(50), or for the maximal response to the GABA(B) agonist baclofen. Furthermore, quantitative receptor autoradiography utilizing (3)H-DAMGO did not reveal any differences in total mu-opioid receptor binding between genotypes. Therefore, we conclude that the complete absence of beta-END throughout development did not alter either the expression of mu-opioid receptors or their coupling to K(+) channels in MBH neurons.
authors.affiliation: Department of Physiology and Pharmacology, Oregon Health Sciences University, Portland, OR 97201, USA.
authors.forename: R M
authors.initials: RM
authors.lastname: Slugg
authors.forename: M D
authors.initials: MD
authors.lastname: Hayward
authors.forename: O K
authors.initials: OK
authors.lastname: Ronnekleiv
authors.forename: M J
authors.initials: MJ
authors.lastname: Low
authors.forename: M J
authors.initials: MJ
authors.lastname: Kelly
mesh_terms: D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology*; D005260:Female; D018755:GABA Agonists / Q000494:pharmacology; D007033:Hypothalamus, Middle / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology; D011333:Pro-Opiomelanocortin / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000819:agonists* / Q000378:metabolism; D012016:Reference Values; D001615:beta-Endorphin / Q000235:genetics / Q000502:physiology*
chemical_list: D018755:GABA Agonists; D015221:Potassium Channels; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D001615:beta-Endorphin; D011333:Pro-Opiomelanocortin; D001418:Baclofen