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

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. © 1990.