Effect of the mu-opioid agonist DAMGO on medial basal hypothalamic neuronsin beta-endorphin knockout mice

The endogenous opioid neurotransmitter beta -endorphin (beta -END), a produ ct of the proopiomelanocortin (POMC) gene, is strongly implicated in the co ntrol of the female reproductive cycle, stress responses, and antinocicepti on. 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, b ut exhibit a significantly attenuated opioid-mediated stress-induced analge sia. To further understand the cellular bases of these responses, we have s tudied 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 posit ive correlation between DAMGO concentration (from 30 nM to 10 muM) and the induced outward K+ current. The genotypes did not differ, however, in eithe r the DAMGO-induced maximum outward current response or EC50, or for the ma ximal response to the GABA(B) agonist baclofen. Furthermore, quantitative r eceptor autoradiography utilizing H-3-DAMGO did not reveal any differences in total mu -opioid receptor binding between genotypes. Therefore, we concl ude that the complete absence of beta -END throughout development did not a lter either the expression of mu -opioid receptors or their coupling to Kchannels in MBH neurons. Copyright (C) 2000 S. Karger AG, Basel.