Chronic aerial exposure to glucorticoids or beta-agonists affects avoidance learning and exploratory motivation in rats

The purpose of the present work was to examine if the conventional asthma treatments in humans (inhalation of glucocorticoids or beta-agonists, administered in a chronic regimen) might affect behavioral processes (learning and exploratory motivation) in rats. Adult male rats were exposed to an atmosphere saturated with either saline, budesonide (a glucocorticoid), or salbutamol (a beta-adrenergic receptor agonist) in a forced ventilation cage, connected to a nebulizer for 5 min twice a day for 15 days at the same hours of the day. Doses of budesonide in the nebulizing solution were 0.116, 1.16, and 11.6 mM. Doses of salbutamol in the nebulizing solution were 1.3, 13, and 130 mM. Forty-eight hours after treatment, the different groups were subjected to exploration of an elevated asymmetric plus-maze (APM, model of exploratory motivation), and 24 h later to learning of an avoidance response to an ultrasonic tone in a two-compartment cage (model of memory and learning). Results showed that budesonide induces moderate effects on exploratory motivation. In one of the fear-inducing arms (single wall arm), exploration decreased and this effect was not dose dependent. In the cognitive model, glucocorticoids affected slightly the latency to escape but with no interference in memory efficiency. On the other hand, at the lower dose in the APM, salbutamol increased significantly the exploration of both fear-inducing arms (no walls and single wall arms). In the learning model, the beta-agonist induced two opposing effects. The lower dose (1.3 mM) facilitated learning and the higher dose (13 mM) inhibited learning instead. In conclusion, results are compatible with the notion that inhaled glucocorticoids or beta-agonists might cross the lung aerial barrier into the blood compartment, exerting effects on learning and motivation functions. (C) 2003 Elsevier B.V. All rights reserved.