K. Lissak

Dose-dependent action of corticosteroids on brain serotonin content and passive avoidance behavior

Abstract Corticosterone, 1.0 and 5.0 mg/kg, improved passive avoidance behavior based on fear versus thirst-conflict situation. Corticosterone, 1.0 mg/kg, increased the serotonin (5-HT) content in the hypothalamus and mesencephalon; 5.0 mg/kg of corticosterone had no effect. Plasma corticosterone level increased in a dosedependent manner after corticosterone treatment. dl -Parachlorophenylalanine (PCPA) impaired passive avoidance behavior and decreased the hypothalamic and mesencephalic 5-HT level. After PCPA treatment, the plasma corticosterone level was slightly increased. PCPA pretreatment was able to prevent the action of 1.0 and 5.0 mg/kg of corticosterone on behavior as well as on brain 5-HT level. Corticosterone, 10.0 mg/kg, impaired passive avoidance behavior, decreased the hypothalamic and mesencephalic 5-HT content, and increased the plasma corticosterone level. Monoamine oxidase inhibitor (nialamide) treatment improved the passive avoidance behavior and increased the 5-HT level in the hypothalamus and mesencephalon. The plasma corticosterone level did not change significantly. Nialamide pretreatment abolished the behavioral action of 10.0 mg/kg of corticosterone as well as its action on brain 5-HT level. A large dose of corticosterone (25.0 mg/kg) and 2.5 mg/kg of 6-dehydro-16-methylenhydrocortisone (6DH) had a similar action on passive avoidance behavior and on brain serotonin level as 10.0 mg/kg of corticosterone; however, the plasma corticosterone level was increased only in corticosterone-treated animals and was significantly decreased after 6DH. 11-Deoxycorticosterone (DOC) at a dose of 25.0 mg/kg was ineffective on passive avoidance behavior and on brain serotonin content, whereas it slightly decreased the plasma corticosterone level. Data suggest that the corticosterone has dosedependent dual action on passive avoidance behavior, and its action is, at least partly, mediated via changed brain serotonin metabolism. The action seems to be a glucocorticoid-specific one since mineralocorticoid (DOC) is ineffective on this behavioral pattern.

Effect of melatonin and pinealectomy on avoidance and exploratory activity in the rat

Abstract Melatonin in a daily dose of 50 μg/rat facilitated the extinction of active avoidance reflex and decreased the intertrial activity during extinction. However, it had no effect on learning and intertrial activity during acquisition. Pinealectomy was ineffective on acquisition, extinction and intertrial activity. Melatonin (100 μg/rat) given in 2 consecutive days facilitated the passive avoidance behavior in water deprived animals in two different experimental situations. Fifty μg of melatonin or pinealectomy was without effect on passive avoidance behavior. Neither melatonin nor pinealectomy had any influence on water intake or on exploratory activity.

5-hydroxytryptamine and the mediation of pituitary-adrenocortical hormones in the extinction of active avoidance behaviour.

Abstract (1) The effect of corticosterone on the extinction of a one-way active avoidance task was correlated with hypothalamic and mesencephalic serotonin (5-HT) content. (2) Corticosterone treatment in a daily dose of 1·0 and 5·0 mg/kg i.p. facilitated the extinction of active avoidance behaviour while doses of 10·0 mg/kg corticosterone delayed it. (3) 1·0 and 2·0 mg/kg corticosterone increased the hypothalamic 5-HT content in normal and adrenalectomized animals, 5·0 mg/kg failed to influence it, and 10·0 mg/kg decreased it. (4) After 1·0, 5·0 and 10·0 mg/kg corticosterone treatment, changes in mesencephalic 5-HT followed a pattern similar to that observed in the hypothalamus. (5) Adrenocorticotrophic hormone (ACTH), in doses of 2·0 and 4·0 i.u./animal, resulted in an increased hypothalamic and mesencephalic 5-HT content in intact animals; however, there were no changes in cerebral 5-HT levels in adrenalectomized rats. (6) Decreased brain 5-HT content, brought about by parachlorophenylalanine (PCPA) (300 mg/kg), was able to prevent the behavioural effect of 1·0 and 5·0 mg/kg corticosterone. (7) PCPA treatment alone given every 72 hr caused a transitory delay in extinction 24 and 48 hr after administration; however, the tendency for extinction to occur did not change. (8) Decreased 5-HT content caused by mesencephalic raphe lesions delayed extinction. (9) Nialamide treatment (125 mg/kg), which increased brain 5-HT content, counteracted the effect of 10·0 mg/kg corticosterone on extinction. (10) These data suggest that the action of corticosterone on active avoidance behaviour is mediated, at least in part, via changed 5-HT metabolism in the brain.

Inhibitory action of midbrain raphe stimulation on stress-induced elevation of plasma corticosterone level in rats

Electric stimulation of rat midbrain raphe nuclei by means of chronically implanted bipolar electrodes was able to reduce the stress-induced increase in plasma corticosterone level by about 40-50%. A serotonin receptor blocker, methysergide, prevented the stimulation-induced inhibition of the stress response. The results support the possible existence of serotoninergic inhibition of hypothalamo-pituitary-adrenocortical activation in rats.

Dose-dependent dual effect of corticosterone on cerebral 5-HT metabolism.

The action of 1.0 and 10.0 mg/kg (i.p.) of corticosterone on serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) contents and on serotonin turnover, measured by an MAO-inhibitor method, was studied at 30 and 120 min after administration. A 1.0 mg/kg dose of corticosterone increased the serotonin content and turnover in the hypothalamus and mesencephalon 30 min after administration; however, it was ineffective on dorsal hippocampus and frontal and parietal cortex. 5-HIAA content did not change significantly in any of the brain areas studied. A 10.0 mg/kg dose of corticosterone decreased the serotonin content and turnover in the hypothalamus and mesencephalon; it was ineffective in other brain areas investigated. 5-HIAA content significantly decreased in the hypothalamus while it increased in the mesencephalon and dorsal hippocampus. In the parietal and frontal cortex, 5-HIAA content did not change following administration of 10.0 mg/kg of corticosterone. At 120 min after corticosterone administration, neither 5-HT content and turnover nor 5-HIAA content showed any change in the brain areas investigated. The results suggest that corticosteroids might change the activity of the brain serotoninergic system in a dose- and time-dependent manner, and in this way the serotoninergic system might play an important role in mediation of the corticosteroid effect exerted on brain function.