BEHAVIORAL AND NEURAL BIOLOGY43, 37-46 (1985) Response of the Rat Brain B-Endorphin System to Novelty: Importance of the Fornix Connection CARLOS A. NETTO, ESPER A. CAVALHEIRO, MARIA A. CARRASCO, NORMA VOLKMER, RENATO D. DIAS, AND IVAN IZQUIERDO 1 Laboratdrio de Neuroqu(mica, Departamento de Bioqu[mica, Inst#uto de Biocidncias, UFRGS (centro), 90,000 Porto Alegre, RS, Brazil In control rats, a step-down inhibitory avoidance training trial using a 0.8 mA footshock, or simple exposure to the training apparatus without footshock, was followed by a decrease of/3-endorphin-like immunoreactivity measured in the hypothalamus and ventral thalamus. The effect of inhibitory avoidance training was also measured in rats submitted to a brain sham operation, to bilateral transection of the dorsal fornix, to anterior or to posterior hypothalamic deaf- ferentation, to adrenal medullectomy, to an adrenal sham operation, to 16 daily ip injections of 0.2 mg/kg dexamethasone, or to 16 daily ip injections of 1 ml/ kg saline. The diencephalic/3-endorphin-like immunoreactivity response to training was abolished by fornix transection and was unaffected by all other treatments. This suggests that the response is not mediated by anterior or posterior neural afferents to the hypothalamus, or by a hypersecretion of epinephrine by the adrenal medullae, or of ACTH by the pituitary gland. The response, instead, appears to require the integrity of the pathway that sends projections from the septo-hippocampal system to the hypothalamus. Previous evidence had suggested that the diencephalic fl-endorphin-like immunoreactivity response to training is a result of novelty, and the septo-hippocampal system has been postulated to play a role in the registration of novelty. © 1985 Academic Press. Inc. /3-Endorphin-like immunoreactivity decreases in the rat brain but not pituitary gland following a variety of behavioral procedures: simple ex- posure to a new environment; inhibitory avoidance training using either a low- (0.3 mA) or a high-intensity (0.8 mA) footshock; testing for retention of inhibitor avoidance with no footshocks; exposure to 30 s of 1.0 mA inescapable footshock; exposure to 50 escapable 1.0-mA footshocks; Research supported by funds from FINEP, PROPESP-UFRGS, and CNPq, Brazil. Professor Esper A. Cavalheiro was on leave from the Departamento de Neurologia e Neurocirurgia, Escola Paulista de Medicina, Sgo Paulo, SP, Brazil. We are thankful to Professor Richard Rodnight, of the Institute of Psychiatry, Maudsley Hospital, University of London, whose generous good offices made the materials used for radioimmunoassay available to us. Send requests for reprints to Dr. Izquierdo. 37 0163-1047/85 $3.00 Copyright © 1985by AcademicPress. Inc. All rightsof reproductionin any form reserved.