Biphasic Effects of Adrenal Steroids on Learned Helplessness Behavior Induced by Inescapable Shock

Abstract

Corticosterone (CS) has been shown to regulate behavior in the learned helplessness (LH) paradigm. Here we provide evidence for a Ushaped relationship between the increasing doses of CS administered and escape failures in the LH model. Replacement with CS (20-400 mg/ml in drinking water) in adrenalectomized (ADX) animals was utilized to examine how the selective activation of mineralocorticoid (MR) and glucocorticoid (GR) receptors is related to the behavioral impairments induced by inescapable shock (IS). Available MR and GR levels were determined in hippocampal cytosol by radioligand binding assays. Non-CS replaced ADX animals showed a high percentage of escape failures assessed 48 h after IS. A CS does of 100 mg/ml given to ADX animals markedly reduced escape failures and resulted in an almost total reduction of available MR associated with a partial reduction of GR. However, the administration of aldosterone (ALDO), a selective MR agonist, was not sufficient to restore normal coping behavior. Moreover, an important role for GR was further shown by means of the specific GR antagonist, RU 38486, which blocked the reduction of LH in ADX rats that were given 100 mg/ml CS. Higher doses of CS given to ADX rats reinstated the LH behavior, and SHAM rats that produced stress CS levels also produced LH behavior. The results indicate a U-shaped dose response function with both negligible and high CS levels being associated with LH behavior. Hence, along with a moderate reduction of available GR level in the cytosol, a large decrease in MR availability seems to be necessary to prevent the acquisition and expression of LH. However, very high reduction of available GR is associated with LH behavior.

Cortisol shifts financial risk preferences

“…In the amygdala, glucocorticoids can cause dendritic arborization (36) and promote corticotrophin-releasing hormone gene expression, with a resulting anxiety (20,37). Together these effects are thought to underlie the observed tendency of chronically stressed individuals to develop a selective attention to negative precedents, to find threat where none exists, and even to experience depression and learned helplessness (20)(21)(22). Although full morphological changes in the brain occur over a long time period, many of the central effects of elevated cortisol, even over an 8-d period, could begin to promote an aversion to uncertainty and potential monetary loss.…”

“…For example, it can contribute to metabolic dysfunction (15) and immunological impairment (16); in the brain, it can impair attentional control and behavioral flexibility (17)(18)(19), and it can promote anxiety (20), depression (21), and learned helplessness (22). These latter effects could be expected to discourage risk taking.…”

Exposure to Stressors during Juvenility Disrupts Development-Related Alterations in the PSA-NCAM to NCAM Expression Ratio: Potential Relevance for Mood and Anxiety Disorders

“…Poor two-way shuttle avoidance performance was observed following both negligible and high doses of injected CORT (Kademian et al, 2005). Selective breeding based on 'high/ low-avoidance' performance was suggested to relate to differences in 'emotional' factors (state/trait anxiety) that influenced performance (Brush, 2003).…”

From molecule to market: steroid hormones and financial risk-taking

“…Under such circumstances, the steroid may have contributed to the extreme levels of risk aversion observed among traders. Indeed, extended periods of uncertainty and uncontrollable stress can promote a condition known as 'learned helplessness', in which persons, and animals, lose all belief in their ability to control or influence their environment (Kademian et al 2005). Under these circumstances, traders could become price insensitive and fail to respond to lower asset prices or interest rates, thereby rendering monetary policy ineffective.…”