Effect of the μ-opioid agonist DAMGO on medial basal hypothalamic neurons in beta-endorphin knockout mice

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 muM) and the induced outward K+ current. The genotypes did not differ, however, in either the DAMGO-induced maximum outward current response or EC50, or for the maximal response to the GABA(B) agonist baclofen. Furthermore, quantitative receptor autoradiography utilizing H-3-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. Copyright (C) 2000 S. Karger AG, Basel.