Hypothalamic histamine release in normal and stressed rats is affected by sex and aging.

Changes in the baseline and in the 40 mM K+-evoked release of histamine from hypothalamus slices were compared in male and female rats aged 2, 6, 12, 18, and 24 months. The baseline release declined in the 12-, 18-, and 24-month males. In contrast, the K+-evoked release remained constant in the males, but in the females it decreased in animals more than 2 months old. The efficiency of the H3 receptors was also determined by measuring the reduction of the K+-evoked release induced by the H3 receptor agonist (R)-alpha-methylhistamine. This substance significantly decreased the amount of HA released in all age groups, except the 24-month-old males. Histamine release was also measured after exposure to a weak electrical stress. In 2- and 6-month-old males, there was a marked reduction of both the baseline and the K+-evoked release, and also of the inhibitory effect of the H3 agonist. There were no changes in the 12- and 18-month age groups, but both releases were enhanced in the 24-month group. In females, electrical stress had no significant effect, except in the youngest age group. Stress-dependent release of plasma corticosterone was decreased in males older than 12 months and in females older than 6 months. These changes gave a good correlation with variation in the H3 receptors. This study, therefore, demonstrates that aging modifies, in a sex-dependent way, the basal and stress-stimulated functions of the hypothalamic presynaptic histaminergic neurons.