Neonatal vitamin K might reduce vulnerability to alcohol dependence in Danish men.

OBJECTIVE: Levels of oxidative defenses and blood-clotting factors are normally reduced in newborns, increasing the risk of injury to developing brain structures around the time of birth. This early neonatal vulnerability corresponds to a timeframe in which the development of reward-related limbic structures is particularly active. Taking advantage of a serendipitous event in the history of treating newborns, we tested the hypothesis that vitamin K supplementation, administered to facilitate the synthesis of blood-clotting proteins within this critical timeframe, might also reduce the development of alcohol dependence later in life. METHOD: Subjects were approximately full-term male infants, selected from a large Danish birth cohort. Two thirds of the original 330 subjects in this study were high-risk sons of alcoholic fathers; 241 of the total completed the 30-year follow-up. Of subjects reported on for this article (N = 238), 44 received vitamin K supplementation at birth; 161 were considered high risk, and 66 were categorized as having lower birth weight (<6 lbs). A comprehensive series of measures was obtained on each subject before, during and shortly after birth as well as at 1 year of age. The Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised, diagnosis of alcohol dependence and a measure of lifetime problem drinking served as the 30-year outcome variables. RESULTS: Vitamin K treatment, inherited risk and low birth weight each independently predicted alcohol dependence and problem drinking at age 30. Vitamin K treatment was associated with significantly lower rates of alcohol dependence and fewer symptoms of problem drinking. CONCLUSIONS: Vitamin K treatment at birth might protect against the development of alcoholism in adults by reducing early postnatal hemorrhage and oxidative brain damage.

Area postrema-lesions increase operant responding to sucrose in rats.

Rats with lesions of the area postrema (APX) are known to exhibit an enhanced intake of highly palatable foods such as sweetened condensed milk and cookies. These observations suggest the possibility that APX rats find these foods more rewarding and will work harder to obtain these foods. Sham and APX rats were tested on fixed ratio (FR) and progressive ratio (PR) schedules. APX rats consistently pressed more times to receive sucrose solution and attained both FR 3 and FR 5 criteria significantly faster than sham-lesioned control rats. Furthermore, rats with APX had significantly higher break points than sham-lesioned control rats on a progressive ratio schedule. These results support the hypothesis that rats with lesions of the area postrema will consistently work harder to obtain a highly palatable food reward.

Cannabinoid agonist, CP 55,940, facilitates intake of palatable foods when injected into the hindbrain.

Cannabinoids have been shown to influence food intake, and until recently, the neural pathways mediating these effects have remained obscure. It has been previously shown that intracerebroventricular injection of delta-9-tetrahydrocannabinol (Delta(9)-THC) causes increased consumption of palatable foods in rats, and we postulated the involvement of the hindbrain in this cannabinoid-induced food intake. Cannulated rats (both female and male groups) trained to consume sweetened condensed milk received either lateral or fourth ventricle injections of CP 55,940 and were presented with sweetened condensed milk 15 min after injection. Rats were injected over a range of doses between 100 pg and 10 microg per rat. Milk intake was recorded for a total of 3 h. Lateral ventricle injection of CP 55,940 increased milk intake at doses in the microgram range. However, CP 55,940 was effective in increasing food intake at nanogram doses when injected into the fourth ventricle. Finally, male rats appeared to be more sensitive to CP 55,940 than female rats inasmuch as milk consumption was increased at the 1 ng dose in male rats, whereas only the 10 ng dose was effective in females. These results indicate that CP 55,940 may act in the hindbrain to influence feeding behavior in rats.

Intracerebroventricular injection of fructose stimulates feeding in rats.

2-deoxy-D-glucose (2DG) inhibits glycolysis and stimulates food intake. Previous work suggests that fructose may attenuate the hyperglycemic and hypothermic effects of 2DG. The current study examined the effect of intracerebroventricular fructose on 2DG-induced feeding. We found that concentrated fructose injected into the cerebroventricles enhanced food intake both in the presence and absence of 2DG. On the other hand, similar concentrations of glucose suppressed 2DG-induced food intake. These data suggest differences in metabolism of glucose and fructose and may provide insight into the metabolic steps monitored by brain glucoreceptors to control food intake.

Area postrema lesions elevate NPY levels and decrease anxiety-related behavior in rats.

Intracerebroventricular administration of neuropeptide Y (NPY) has been shown to reduce anxiety-like effects in rodents and also profoundly alter feeding. The area postrema-lesioned (APX) rat model of food motivated behavior overconsumes palatable foods and expresses significantly higher levels of NPY in the hypothalamus than sham-lesioned control rats. For this reason, we examined APX rats in the open field test, which is a standard measure of anxiety- or fear-related behavior and also investigated NPY mRNA levels in the hippocampus, amygdala and hypothalamus. We found that APX rats display reduced anxiety-like behavior in the open field test as indicated by spending increased time in the center of the field as opposed to the perimeter of the field. NPY mRNA levels were also found to be significantly elevated in the amygdala, hippocampus and arcuate nucleus of the hypothalamus of APX rats when compared to sham-lesioned rats. These results support the action of limbic NPY to reduce anxiety-like behavior in a rodent model that appears to express higher than normal NPY levels.