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.
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Millhauser Laboratories, Department of Psychiatry, New York University Medical Center, NY 10016.
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D000818:Animals; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D004399:Dynorphins / Q000276:immunology / Q000502:physiology*; D004558:Electric Stimulation; D005247:Feeding Behavior / Q000187:drug effects* / Q000502:physiology; D007106:Immune Sera / Q000494:pharmacology; D007276:Injections, Intraventricular; D008297:Male; D010446:Peptide Fragments / Q000276:immunology / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains
D007106:Immune Sera; D010446:Peptide Fragments; D004399:Dynorphins; C026770:dynorphin (1-8)