Beta-adrenergic Receptors Are Involved in Stress-related Behavioral Changes

Cerebral noradrenergic systems have been implicated in stress-related changes in behavior. Previous studies with receptor antagonists suggested that alpha 1-adrenergic receptors were involved in defensive withdrawal in rats and in investigatory behavior in mice tested in the multicompartment chamber. However, beta-adrenoreceptor antagonists attenuated the restraint- and ICV CRF-induced changes in defensive withdrawal, suggesting that beta-adrenergic receptors may also be involved in stress-related responses. To determine whether the beta-adrenergic antagonist effect was limited to rats tested in the defensive withdrawal model, we studied the effects of L-propranolol in two other behavioral models. Propranolol pretreatment (2.5 mg/kg, IP) prevented the restraint-induced changes in the behavior of mice observed in the multicompartment chamber and the elevated plus-maze. It also decreased the plasma corticosterone response measured in restrained mice after plus-maze testing. To investigate further the role of central beta-adrenergic receptors in defensive withdrawal, the effects of the beta-adrenoreceptor agonist isoproterenol were tested. Isoproterenol (0.3-10 micrograms, ICV) produced a dose-dependent increase in defensive withdrawal, statistically significant after 3 and 10 micrograms. Propranolol prevented the isoproterenol-induced defensive withdrawal, suggesting that the effect of isoproterenol resulted from stimulation of beta-adrenergic receptors. These results support earlier data suggesting the involvement of CNS beta-adrenergic receptors in stress-related behavioral changes and suggest that beta-adrenergic agonists exert anxiolytic effects that differ from those of the benzodiazepines.