Short communication NORADRENERGIC STIMULATION OF THE LATERAL HYPOTHALAMUS AS A REINFORCEMENT IN T MAZE LEARNING IN RATS

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ACTA NEUROBIOL. EXP. 1978, 38: ROM13 Short communication NORADRENERGIC STIMULATION OF THE LATERAL HYPOTHALAMUS AS A REINFORCEMENT IN T MAZE LEARNING IN RATS Jerzy CYTAWA and Edyta JURKOWLANIEC Department of Physiology, Institute of Medical Biology, School of Medicine Gdalisk, Poland Since the time when Olds and Milner (15) have discovered that electrical stimulation of certain brain areas can serve as a reinforcement for motivated behavior, it has been shown that electrical stimulation of certain areas within the lateral hypothalamus evoked both self-stimulation and eating responses (14). These data became the basis for the view that drive induction rather than drive reduction constitutes the reinforcement of motivated behavior. Besides electrical stimulation the alimentary drive can also be induced by noradrenergic stimulation of certain loci with the hypothalamus (3, 4, 8-12, 20). If drive induction does have reinforcing properties for motivated behavior, this noradrenergic stimulation should have reinforcing properties as well. The aim of our paper was to verify this assumption. The experiment was carried out on 5 male hooded rats weighing 250-300 g. The animals were permanently implanted with bilateral cannulas aimed at the perifornical region of the anterior part of the lateral hypothalamus (LH). Chronic cannulas were implanted stereotaxically under Nembutal anesthesia, according to the procedure described in detail by Slangen and Miller (20) with the use of the following coordinates: 0.0 mm (bregma) anterior, 1.3 mm lateral and 8.2 rnrn vertical with the teeth bar 3.1 mm above the intra-aural line. This part of the brain is known to elicit a reliable eating response to noradrenergic stimulation (20) in sated rats. Noradrenaline (NA) was

given in 0.5 pl injections containing 60 nmoles (21 pg) of 1-noradrenaline bitartrate (Chemie Limz Ag, Austria) dissolved in normal saline. Experiments were conducted daily on food and water sated animals, always at the same time (10 a.m.). In the control experiment the effects of unilateral NA injection with respect to eating response were tested and compared to those of unilateral injection of 0.5 p1 of normal saline used as a vehicle. For this purpose each cannula was tested twice for effects of NA and twice for effects of saline, injected in a counterbalanced sequence once a day. During the control experiment as well as later during the chemostimulation experiment in a T maze situation, free access to chow pellets and water was given for 45 min after injection and the chow intake was then measured. After completion of the control experiment all rats were given 10 choices in the T maze, one a day, in order to find their natural preference for one of the two arms of the maze. Then, the chemostimulation experiment began, which also lasted 10 days. Each choice of the previously ncmpreferred side of the T maze was reinforced with an NA injection to the perifornical LH, while chosing the other arm was followed with a saline injection through the same cannula. As shown in Fig. 1 NA injected in the control experiment evoked a marked eating response of 2.00 f 0.22 g. Saline injected through the 2.5 1 I Norodrenaline NaCl t CONTROL^ 1 2 3 1. 5 6 7 8 1 SUCCESSIVE CHEMOSTIMULATION I NA or NaCI) int MAZE SITUATION Fig. 1. Effect of noradrenergic stimulation of the hypothalamus on food intake (mean k SE, n = 5).

same cannula gave no eating response or a negligible one, amouting to 0.03 f 0.02 g (P < 0.001). Eating response to NA remained virtually unchanged till the end of the experiment. W G BEF3RE NORAORENERGIC STIMULATION WITH NORADRENERGIC STIMULATON ( nonpreferred s~de 1s re~nforced w~th MA),,, 8,,,,,, 1 6 7 DAYS 10 I,,,, I I I 1 i 1 4 7 DAYS 10 Fig. 2. Effect of noradrenergic stimulation of the hypothalamus on reversal of preference in T maze (n = 5). Figure 2 shows that in a T maze situation spontaneous preference for one of the two arms of the maze established itself gradually, and finally in the last two days none of the rats chose the nonpreferred side. The chemostimulation experiment caused all the rats to change their preference rapidly. Once they happened incidentally to go to the previously nonpreferred side of the T maze and to receive an NA injection (this event is marked by a broken line in Fig. 2), they chose that particular side with daily increasing frequency. The results obtained prove that NA-induced activation of the alimentary drive has an obvious reinforcing effect in motivated behavior. This effect is similar to that obtained in other experiments when electrical stimulation of some brain areas, the LH inclusive, evoked both selfstimulation and eating responses (14). Since our experiment was perfcrmed on sated animals, AN-induced activation of the alimentary drive could not be attributed to metabolic changes but rather to a central nervous precess which enhances the attractiveness of gustatory stimuli, both actual and their memory traces. Presumably, intrahypothalamic NA injections influence the process of hedonesthesia recently postulated by Cytawa and Trojniar (7), i.e., the central nervous process which determines the hedonic value of stimuli, and which therefore allows to experience pleasure. If so, our results may support the hedonic theory of

motivated behavior (5, 6, 16, 25) which claims that the search for pleasure is the main drive for all motivated appetitive behavior. They also strongly favor the view that NA serves as a neurotransmitter released by those neurons that form the so-called reward system (1, 2, 13, 17-19, 21-24), which according to Cytawa and Trojniar (7) is in fact the pleasure system of the brain. This investigation was supported by Project 10.4.1.01.5.3 of the Polish Academy of Sciences. ANLEZARK, G. M., CROW, T. J. and GREENWAY, A. P. 1973. Impaired learning and decreased cortical norepinephrine after bilateral locus coeruleus lesions. Science 181: 682-684. BELLUZZI, J. D., RITTER, S., WISE, S. D. and STEIN, L. 1975. Substantia nigra self-stimulation: Dependence on noradrenergic reward pathways. Behav. Biol. 13: 103-111. BOOTH, D. A. 1967. Localization of the adrenergic feeding system in the rat diencephalon. Science 158: 515-516. BOOTH, D. A. 1968. Mechanism of action of norepinephrine in eliciting an eating response on injection into the rat hypothalamus. J. Pharmacol. E,xp. Ther. 160: 336-348. CABANAC, M. 1971. Physiological role of pleasure. Science 173: 1103-1107. CYTAWA, J. and TROJNIAR, W. 1976. The state of pleasure and its role in instrumental conditioning. Act. Nerv. Super. 18: 92-96. CYTAWA, J. and TROJNIAR, W. 1978. Hedonesthesia: The nervous process determining motivated ingestive behavior. Acta Neurobiol. Exp. 38: 139-152. GROSSMAN, S. P. 1960. Eating or drinking elicited by direct adrenergic or cholinergic stimulation of hypothalamus. Science 132: 301-302. GROSSMAN, S. P. 1962. Direct adrenergic and cholinergic stimulation of hypothalamic mechanisms. Am. J. Physiol. 202: 872-882. LEIBOWITZ, S. F. 1970. Hypothalamic fj-adrenergic "satiety" system antagonizes an a-adrenergic "hunger" system in the rat. Nature 226: 963-964. LEIBOWITZ, S. F. 1970. Reciprocal hunger-regulating circuits involving alpha- and beta-adrenergic receptors located, respectively, in the ventromedial and lateral hypothalamus. Proc. Natl. Acad. Sci. USA 67: 1063-1070. MARGULES, D. L. 1969. Initiation and suppression of feeding behavior by adrenergic receptors in rat brain. Physiologist 12 : 293. MARGULES, D. L. 1969. Noradrenergic rather than serotonergic basis of reward in dorsal tegmentum. J. Comp. Physiol. Psychol. 67: 32-35. MARGULES, D. L. and OLDS, J. 1962. Identical "feeding" and "rewarding" systems in the lateral hypothalamus of rats. Science 135: 374-375. OLDS, J. and MILNER, P. 1954. Positive reinforcement produced by electrical stimulation of the septa1 area and other regions. of the brain. J. Comp. Physiol. Psychol. 47: 413-427. PFAFFMANN, C. 1960. Pleasures of sensations. Psychol. Rev. 67: 253-268. POSCHEL, B. P. H. and NINTEMAN F. W. 1963. Norepinephrine: A possible excitatory neurohormone of the reward system. Life Sci. 2: 782-788.

18. RITTER, S. and STEIN, L. 1973. Self-stimulation of noradrenergic cell group (A61 in the locus coeruleus of rats. J. Comp. Physiol. 85: 443452. 19. RITTER, S. and STEIN, L. 1974. Self-stimulation in the mesencephalic trajectory of the ventral noradrenergic bundle. Brain Res. 81: 145-157. 20. SLANGEN, J. L. and MILLER, N. E. 1969. Pharmacological tests for the function of hypothalamic norepinephrine in eating behavior. Physiol. Behav. 4: 543-552. 21. STEIN, L. 1968. Chemistry of reward and punishment. In D. H. Efron (ed.), Pharmacology: A review of progress 1957-1967. Public Health Service, Washington, D. C. p. 105-123. 22. STEIN, L. 1975. Norepinephrine reward pathways: Role in self -stimulation, memory consolidation and schizophrenia. In J. K. Cole and T. B. Sonderegger (ed.), Nebraska Symposium on Motivation. Univ. of Nebraska Press, Lincoln, p. 113-159. 23. STEIN, L. 1978. Reward Transmitters: Catecholamines and Opioid Peptides. In M. A. Lipton, A. DiMascio and K. F. Killam (ed.), Psychopharmacology: A Generation of Progress. Raven Press, New York, p. 569-581. 24. WISE, C. D., BERGER, B. D. and STEIN, L. 1973. Evidence of a-noradrenergic reward receptorq and serotonergic punishment receptors in the rat brain. Biol. Psychiatr. 6: 3-21. 25. YOUNG, P. T. 1959. The role of affective processes in learning and motivation. Psychol. Rev. 66: 104-125. Accepted 20 February 1978 Jerzy CYTAWA and Edyta JURKOWLANIEC, Institute of Medical Biology, School of Medicine, Debinki 1, 80-211 Gdansk, Poland.