Modulation of isolation-induced fighting by N- and C-terminal analogs of substance P: Evidence for multiple recognition sites

Abstract

Substance P (SP) significantly reduced fighting in mice made aggressive by prolonged isolation. The N-terminal heptapeptide fragment SP (1–7) also reduced fighting. The C-terminal fragment SP(4–11) was without activity, while the shorter C-terminal fragment analog <E-SP(7–11) significantly increased isolation-induced fighting. The aggression-enhancing effect of <E-SP(7–11) was antagonized by naloxone, which by itself had no significant effect. The aggression-reducing effect of SP(1–11) was significantly enhanced by naloxone, while the effect of SP(1–7) was unchanged. These results demonstrate that a behavioral effect of SP may be duplicated by an N-terminal fragment of the SP molecule, and that peptide fragments or analogs of the N- and C-terminal portions of the SP molecule can exert opposing effects on a specific behavior. These findings represent a structure/activity relationship that is strikingly different from any previously described for SP. The differeing effects of naloxone on N- and C-terminal fragment analogs suggest that these two effects may be mediated by different mechanisms.