β-Adrenergic receptor subtypes in stress-induced behavioral depression

Abstract

The purpose of this study was to examine the role of β-adrenergic receptors in an animal model of stress-induced behavioral depression. β-Adrenergic receptors in several brain regions and leukocytes of rats were determined by receptor binding techniques using 125I-cyanopindolol (cyp) as ligand and propranolol as displacer for total β-adrenergic receptors, and ICI 86,406 for β 1- and ICI 118, 551 for β 2-adrenergic receptors. We observed that the maximum number of binding sites ( B max) and the apparent dissociation constant ( K d ) of 125I-cyp binding to total β-adrenergic receptors were increased in hippocampus of stressed rats with escape deficits (48 h after training) as compared to control rats. This increase was due to an increase in B max and K d of 125I-cyp binding to β 1-adrenergic receptors but not to β 2-adrenergic receptors. There was no significant difference in β 1-adrenergic receptors in cortex and cerebellum or β 2-adrenergic receptors in hippocampus, cortex, cerebellum, or leukocytes of stressed (48 h after training) rats with escape deficits as compared to control rats. Interestingly, it was observed that β 1- and β 1-adrenergic receptors in various brain regions (cortex, cerebellum, and hippocampus) and β 2-adrenergic receptors in leukocytes of stressed rats (10 days after training) were not significantly different from control rats, although escape deficits were still present. These results suggest that abnormalities in adrenergic neurotransmission are associated with an upregulation of β 1-adrenergic receptors, which in turn may be involved in the early stages of behavioral deficits caused by uncontrollable shock.