Psychopharmacology 64, 41-43 (1979) Psychopharmacology 9 by Springer-Verlag 1979 The Effect of Bilateral Ventral Noradrenaline Bundle Lesions on Lever Pressing for Food in Rats Z. L. Kruk 1 and J. Millar 2 1 Department of Pharmacology and Therapeutics, and 2 Department of Physiology, The London Hospital Medical College, Turner Street, London E1 2AD, U.K. Abstract. Food reward has been associated with acti- vation ofnoradrenergic mechanisms in the brain. Using rats trained to press a lever for food reward, we have investigated the effects of 6-hydroxydopamine lesions, which severly depleted hypothalamic noradrenaline, on the willingness of the rats to press the lever for food reward. We found that performance in the food- rewarded task was significantly impaired following such lesions, and that this was especially marked when the task was made more difficult. From our results we suggest that ventral noradrenaline bundle lesions can decrease the rewarding nature of food, thus making the animals less willing to work for food reward. Key words: Ventral noradrenaline bundle - 6-OHDA lesions - Food - Reward The distribution of noradrenaline (NA) in the rat brain has been extensively studied, and it is currently accepted that there are three main groups of NA- containing axons. The dorsal bundle arises from neurones with cell bodies in the midbrain in the region of the locus ceruleus, and ascends to innervate mainly the neocortex and hippocampus. Recent studies indicate that this patway may be concerned wih learning and exploratory behaviour (Mason and Fibiger, 1977; Mason and Iversen, 1975). A descending pathway from the mid- brain innervates the spinal cord with functions proba- bly concerned with cardiovascular control and control of tone of voluntary muscle (Bolme et al., 1972; Anden et al., 1966). A ventral ascending noradrenergic bundle has also been described with nerve cell bodies situated ventral to those of the dorsal bundle, and with axons terminating in the hypothalamus and amygdala (Ungerstedt, 1971). Among the roles proposed for hypothalamic NA has been the control of feeding. Grossman (1960) showed that NA, injected through a microcannula into the brains of satiated rats, could elicit vigorous feeding, and this observation has frequently been verified by other authors (see review by Leibowitz, 1976). The role of NA in the normal control of feeding is however controversial. Studies using the neurotoxin 6-hydroxydopamine to deplete hypothalamic NA have demonstrated hyperphagia in rats (Ahlskog and Hoebel, 1973; Ahlskog, 1974). Other work, based on self-stimulation experiments, has implied that acti- vation of NA neurones could act as a reward in the brain (Kelly et al, 1974). Feeding can be regarded as a rewarding activity, and it seemed possible that the effects of NA on feeding could be due to the activatin of a reward system normally triggered by the feeding behaviour itself. To test this hypothesis we have carried out experiments in which we have lesioned the ventral noradrenergic bundle, using 6-hydroxydopamine (6-OHDA), and tested the performance of the animals on a food- rewarded task. Materials and Methods Ten male Sprague-Dawley rats were trained in a Skinner box to push a lever for a food pellet reward, receivingone pellet per bar push. This schedule is henceforth referred to as FRI. Each rat was food-deprived for 20 h before a daily 30-rain training session, after which he was allowed free accessto food for 3.5 h. After each session the number of pellets delivered was noted and the animals were weighed. When the animals had stabilised at a steady rate of lever pressing they were anaesthetised (50 mg sodium methohexitone/kg i.p.) and placed in a stereotaxic frame. Mean body weights at the time of operation were 200.0 g (n = 5, SE 5.2) (controls) and 204.0 g (n = 5, SE 9.3) (experimentals). Five of the animals received bilateral injections of 16~tg 6-OHDA in 2p.1 nitrogen-bubbled water containing ling ascorbic acid/ml at co-ordinates A 1 ram, L 2.5 ram, V 2.8 ram, above HZP (Konig and Klippel, 1963). The other five animals received 6-OHDA-free injections at the same co-ordinates. After operation the animals continued the daily 30-rain test sessions. All sessions were now carried out by an operator who did not know which animals had received 6-OHDA. After 10 days the animals were switched to a schedule which required three lever pushes for each 0033-3158/79/0064/0041/$01.00