The selective kappa agonist U-50,488H was evaluated on the elevated plus-maze test of anxiety. U-50,488H was administered intraperitoneally to male Sprague-Dawley rats 20 min before testing, first in an open field apparatus, then followed immediately on the elevated plus-maze. No significant change in spontaneous locomotor activity was measured in the open field apparatus, suggesting that U-50,488H was devoid of sedative effects in the dose range tested (0.1-1000 micrograms/kg, IP). Doses between 10 and 1000 micrograms/kg produced significant increases in elevated plus-maze behavior that were consistent with anxiolytic actions for U-50,488H. These anxiolytic-like effects were antagonized by naloxone (2.0 mg/kg, IP), suggesting an opioid receptor site of action. In addition, we tested the kappa 1-selective U-50,488H-derivative, U-69,593 (100 micrograms/kg, IP), which was also shown to mimic the anxiolytic-like effects produced by U-50,488H. These results suggest that low doses of the selective kappa 1 agonists U-50,488H and U-69,593 are endowed with anxiolytic properties in rodents and that the kappa opioid system may be involved in the behavioral response to anxiety.

After injection of [3H]-1,25(OH)2-vitamin D3 (soltriol), nuclear labeling is found in Sertoli cells of testes, being highest at the stage of spermiosis, in epithelium of efferent ductules and caput epididymidis and in connective tissue cells of epididymis, in lamina propria and muscular sheath of deferent duct, and in epithelium and muscular sheath of dorsal and ventral prostate of the mouse. This labeling pattern is characteristic for [3H]-soltriol and differs from that for [3H]-dihydrotestosterone and [3H]-estradiol, although with overlap. The nuclear labeling with [3H]-soltriol suggests an action of the hormone on certain processes during spermatogenesis, on sperm maturation, on epididymal fluid resorption, and on secretion and transport of spermatozoa.

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This is a review and a prospectus of effects of vitamin D on the brain. Effects of sunlight and equivalent artificial light on physiological and behavioral processes are probably mediated, in large part, through the skin-vitamin D-endocrine system. Experimental evidence from our laboratory reveals sites of action and concomitant direct effects of 1,25(OH)2 vitamin D3 (soltriol) on brain, spinal cord, pituitary and other endocrine tissues. This appears relevant for the activation and modulation of mental and endocrine processes, particularly related to seasonal and daily biorhythms. Effects of sunlight and corresponding artificial light are likely to be mediated through direct actions of soltriol on brain and endocrine tissues that are independent of its effect on calcium levels. Those direct actions are receptor mediated and appear to be dose related as they depend on intensity of light and length of exposure, considering light (photons) as a drug. A role for soltriol, the steroid hormone of sunlight, in the etiology and helio- or phototherapy of affective disorders with cyclic seasonal onset (seasonal affective disorder) is discussed and the significance of research in the new frontier of vitamin D and brain relationships is noted.