In rats anesthetized with pentobarbital, increments in corticosterone concentration were elicited upon electrical stimulation through chronically implanted electrodes. Prestimulation steroid levels were low. Poststimulation levels varied according to the site stimulated. These sites, ranging in order of responsiveness from greatest to least, were amygdala, mammillary hypothalamus, tuberal hypothalamus, and preoptic area. The corticosterone increments obtained under anesthesia were similar in magnitude to those obtained in the absence of anesthesia. Placement of the electrodes in the median eminence itself did not enhance the responsiveness. Hind leg shock evoked a steroid increment comparable to that produced by tuberal stimulation ; and ketamine, a centrally acting drug, provided an estimate of the maximal centrally elicited response. The evidence is consistent with the view that excitatory afferent paths to corticotropin releasing factor (CRF) neurons and the CRF neurons themselves lie distributed in the tissue stimulated.

Lesions in the lateral hypothalamus produced by high frequency currents result in an immediate decrease in rate and/or depth of respiration in lightly anesthetized cats. The effect increases with the size and number of such lesions; even unilateral lesions are effective. The blood pressure and heart rate are decreased slightly at the same time. If the respiration declines markedly, compensatory regulations due to asphyxia occur which raise the blood pressure and restore respiration. Bilateral injections of barbiturates into the lateral hypothalamus are followed by a reversible reduction in respiratory activity. It is concluded that impulses from the lateral hypothalamus exert a tonic facilatatory action on the respiratory center.

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In the search for ways to augment current brain tumor therapies many have sought to exploit the fact that adult brain tissue is virtually lacking in cell division. This endorses a special appeal to therapeutic approaches which target the dependence on cell division for brain tumor growth. Polyamines play an essential role in the proliferation of mammalian cells and depletion results in inhibition of growth. As a result, there are investigations into the feasibility of controlling tumor growth by targeting the enzymes in polyamine metabolism with specific enzyme inhibitors. DFMO, an inhibitor of putrescine synthesis, is a cytostatic agent which in combination with tritiated radioemitters or cytotoxic agents such as, MGBG or BCNU is an effective antitumor agent, but the effectiveness of DFMO in vivo is reduced by tumor cell uptake of polyamines released into the circulation by normal cells and from gut flora or dietary sources. However, DFMO therapy combined with elimination of exogenous polyamines inhibits tumor growth but also results in body weight loss, reduced protein synthesis and evidence of toxicity. Furthermore, tumor growth recurs upon termination of treatment. In contrast, competitive polyamine analogs function in the homeostatic regulation of polyamine synthesis but fail to fulfill the requirements for growth and they continue to inhibit tumor growth for several weeks after cessation of treatment. Analogs are now in clinical trials. However, their action may be highly specific and differ from one cell type to another. We suggest that the effectiveness of polyamine based therapy would be enhanced by two approaches: local delivery by intracerebral microdialysis and tumor cell killing by internal radioemitters such as tritiated putrescine or tritiated thymidine which are taken up in increased amounts by polyamine depleted tumor cells. The growth inhibition by polyamine depletion prevents the dilution of the radioactive putrescine and thymidine. The overload of radioactivity kills the growth inhibited cells so that growth cannot recur when treatment terminates.