Abstract

Both C-terminal fragments of lipotropin (beta-LPH) (endorphins) and N-terminal fragments (e.g., ACTH 4-10) delayed extinction of pole-jumping avoidance behavior in rats. After subcutaneous injection Met5-enkephalin appeared to be as active as ACTH 4-10 whereas beta-LPH 61-69, alpha- and beta-endorphin were more potent in delaying extinction of pole-jumping avoidance behavior (approximate ED50 of alpha-endorphin 4 x 10(-11) M rat.) However, the potency of beta-LPH 61-69 and alpha-endorphin appeared to be approximately the same whereas that of beta-endorphin was less than that of ACTH 4-10 after intraventricular administration (approximate ED50 of alpha-endorphin 0.2 x 10(-11) M rat). alpha-Endorphin and ACTH 4-10, administered subcutaneously in a dose which markedly delayed extinction of pole-jumping avoidance behavior, had only slight effects on open field behavior and on responsiveness to electric footshock. A 5 times higher dose of both peptides facilitated passive avoidance behavior. Morphine in two doses significantly delayed extinction of pole-jumping avoidance behavior but the effect was not dose dependent. The specific opiate antagonist naltrexone, however, markedly facilitated extinction of the avoidance response. ACTH 4-10, alpha- and beta-endorphin and a behaviorally potent ACTH 4-9 analog (Org 2766) restored pole-jumping avoidance behavior of rats pretreated with naltrexone. Treatment with a similar dose of naltrexone blocked beta-endorphin-induced analgesia. These results suggest that the influence of peptides related to C-terminal and N-terminal fragments of lipotropin on extinction of avoidance behavior may be dissociated from those exerted on opiate receptor sites. Subcutaneously injected beta-LPH 61-69 or intraventricularly administered beta-endorphin induced a shift from lower to higher frequencies of hippocampal theta rhythm during paradoxical sleep in the same way as that found after ACTH 4-10. This effect is interpreted as indicating an increased arousal state in certain midbrain limbic structures. This may, as has been postulated for ACTH 4-10, alter the motivational value of environmental stimuli (e.g., aversive stimulation).