Rostral and caudal ventricular infusion of antibodies to dynorphin A(1–17) and dynorphin A(1–8): effects on electrically-elicited feeding in the rat

Abstract

Lateral ventricular injection of antibodies to dynorphin A(1–13) was previously shown to elevate lateral hypothalamic stimulation frequency threshold for eliciting feeding behavior. The antibodies utilized in that study cross-react completely with dynorphin A(1–17) and, to a lesser extent, dynorphin A(1–8). In the present study, highly specific antibodies to dynorphin A(1–17) and dynorphin A(1–8) were infused into the lateral ventricle and mesopontine aqueduct to determine which biologically active dynorphin A fragment mediates feeding and at what level of the CNS this activity is likely to occur. Both antibodies were found to elevate the feeding threshold. Dynorphin A(1–8) antibodies were effective at both injection sites while dynorphin A(1–17) antibodies were only effective at the lateral ventricular site. These findings suggest that feeding-related dynorphin A(1–17) activity may occur predominantly within the forebrain, while dynorphin A(1–8) activity occurs within the brainstem. Only the dynorphin A(1–8) antibodies, infused into the aqueduct, produced a naloxone-like pattern of progressive elevation in serially determined thresholds; this pattern was previously interpreted to reflect a reduction in consummatory reward. Dynorphin A(1–8) activity within some brainstem structure(s) may therefore contribute prominently to the opioid mechanism whose mediation of the hedonic response to food was previously inferred from naloxone antagonism.