CENTRAL AUTONHMIC MECHANISMS 



969 



hypotlialamus and perhaps in the upper part of the 

 midbrain may lead to an increased sensitivity to 

 insuHn (157). Since profound disturbances in growth 

 occur in rats with such lesions, some evidence is added 

 that the anterior hormone concerned with carbo- 

 hydrate metabolism is related to the growth hor- 

 mone; and the administration of the growth hormone 

 appears to reduce the insulin sensitivity of experi- 

 mental animals with hypothalamic lesions. The lesions 

 which ameliorate experimental diabetes meliitus or 

 increase sensitivity to insulin may be widely varied 

 and scattered, and careful examination of these 

 lesions in the hypothalamus in a large number of 

 animals by the author and his colleagues has not 

 presented any evidence of specific localization. The 

 results suggest, however, that hypothalamic injury 

 may disturb the production or release of such pitui- 

 tary principles as are concerned in carijohydrate 

 metabolism. 



Hxpntlwlnmus and Behavior 



We are here concerned with such types of behavior 

 patterns as are involved in sexual activity, the secur- 

 ing of food, generalized emotional responses and 

 states of wakefulness and sleep. 



SEXUAL BEHAVIOR. There are cases, both clinical and 

 experimental, in which sexual behavior is abnormal 

 or deficient even in the presence of an intact pituitary 

 and gonads. Experimental work indicates that the 

 estrual iiehavior pattern does not appear in animals 

 in which the caudal portion of the hypothalamus, 

 plus the upper part of the midbrain, have been de- 

 stroyed despite administration of pituitary or gonadal 

 hormones in cjuantities sufficient to arouse sexual 

 behax'ior in normal animals (13). Normal patterns 

 of sexual activity may appear upon hormonal treat- 

 ment after removal of the neocortex and much of the 

 olfactory areas, however. In human individuals, cases 

 of idiopathic amenorrhoea and frigidity have fre- 

 quently been ascribed to emotional disturbances 

 which may possibly interfere with hypothalamic 

 activation of the pituitary (6). It has been noted 

 abo\e that sufficiently extensive lesions of the poste- 

 rior part of the tuber may produce gonadal atrophy. 

 It must not be forgotten that normal sexual behavior 

 depends upon neural patterns activated or otherwise 

 influenced by appropriate hormones. This subject is 

 considered further in Chapter XLIX of this volume 

 by Sawyer. 



.\PPETITE .^ND OBESITY. The classical description of 

 adiposogenital dystrophy as a hypothalamic phe- 

 nomenon is very familiar and the term 'hypothalamic 

 obesity' has received much use. It is true that obesity 

 may be associated with hypothalamic disease, often 

 caused by encroachment by hypophysial tumors, and 

 so may genital dystrophy; but the two are not neces- 

 sarily inseparable. It is likely that both lower food 

 requirements and overconsumption of food contribute 

 to hypothalamic obesity. There is excellent evidence 

 that experimental lesions in the ventromedial portions 

 of the tuber in animals are associated with excessive, 

 even ravenous appetite and with hyperphagia which 

 result in extreme obesity if unrestricted access to food 

 is permitted (86). It is not clear whether this glut- 

 tonous disposition is due to changes in visceral activity 

 or whether satiety may be prevented, or appetite 

 released or facilitated by these lesions. The lesions 

 may be quite restricted and have been found invari- 

 ably to be within the boundaries of the ventromedial 

 nuclei. Striking evidence that this nucleus may be 

 concerned in appetite or satiety is presented by 

 Marshall et a!, (i 10) who injected gold thioglucose in 

 a certain strain of mice. This substance caused exten- 

 sive damage to the ventromedial nuclei with resulting 

 obesity. 



If a balance exists between an inhibitory zone in 

 the ventromedial nucleus and a separate activating 

 mechanism for appetite, the question arises as to 

 where the latter may be located. Anand & Brobeck 

 (5) have presented evidence that i^ilateral destruction 

 of rather small areas in the lateral hypothalamic 

 region does away with appetite, and it has been known 

 for some time that extensive lateral and posterior 

 hypothalamic lesions are not consistent with volun- 

 tary taking of food. Larsson (loi) stimulated the 

 lateral hypothalamic regions in goats and produced 

 hyperphagia; during the actual stimulation, oral feed- 

 ing pattern movements were elicited. Forssberg & 

 Larsson (54) studied the distribution of certain in- 

 jected isotopes in the hypothalamus in hungry and fed 

 rats and found e%iclence for increased absorption of 

 such isotopes in this area in hungry animals. They 

 suggest that changes in the concentration of adenosine- 

 triphosphate and creatine phosphate in the region 

 may be a driving force for appetite. 



A somewhat similar mechanism for drinking be- 

 havior has l:)een postulated. Andersson & McCann 

 (7, 8) found that stimulation in the dorsal hypo- 

 thalamic region in goats caused increased drinking 

 as well as evidence of milk ejection and antidiuresis. 

 They also found that certain lesions in dogs would 

 produce hypodipsia. Greer (66) also found that 



