Lack of the involvement of μ1-opioid receptor subtype on motivational effects induced by the endogenous μ-opioid receptor ligands endomorphin-1 and-2 in the mouse

The present study was designed to investigate the role of mu -opioid receptor subtypes in the motivational effect of endogenous mu -opioid receptor ligands, endomorphin-1 and -2. In C57BL/6J mice, endomorphin-1 produced a significant place preference, whereas endomorphin-2 exhibited a significant place aversion. These effects were abolished by a mu (1)/mu (2)-opioid receptor antagonist beta -funaltrexamine. Under these conditions, both endomorphin-1 and -2 produced their motivational effects in mu (1)-opioid receptor-deficient CXBK mice, indicating the mu (2)-opioid receptor involvement. Furthermore, in the lower midbrain including ventral tegmental area, both endomorphin-1 and -2 equally produced dose-related increases in guanosine-5'-o-(3-[S-35] thio) triphosphate bindings in C57BL/6J and CXBK mice. These findings indicate that endomorphin-1 and -2 may produce distinct motivational effects via respective mu (2)-opioid receptor isoforms in the mouse. Furthermore, endomorphin-1 and -2 produced the yl-resistant G-protein activation in the mouse lower midbrain. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.