Examination of the Role of Adrenergic Receptor Stimulation in the Sensitization of Neuroinflammatory-Based Depressive-Like Behavior in Isolated Guinea Pig Pups

Stress. 2023 Aug 2:1-16. doi: 10.1080/10253890.2023.2239366. Online ahead of print.ABSTRACTEarly-life attachment disruption appears to sensitize neuroinflammatory signaling to increase later vulnerability for stress-related mental disorders, including depression. How stress initiates this process is unknown, but studies with adult rats and mice suggest sympathetic nervous system activation and/or cortisol elevations during the early stress are key. Guinea pig pups isolated from their mothers exhibit an initial active behavioral phase characterized by anxiety-like vocalizing. This is followed by inflammatory-dependent depressive-like behavior and fever that sensitize on repeated isolation. Using strategies that have been successful in adult studies, we assessed whether sympathetic nervous system activity and cortisol contributed to the sensitization process in guinea pig pups. In Experiment 1, the adrenergic agonist ephedrine (3 or 10 mg/kg), either alone or with cortisol (2.5 mg/kg), did not increase depressive-like behavior or fever during initial isolation the following day as might have been expected to if this stimulation was sufficient to account for the sensitization process. In Experiment 2, both depressive-like behavior and fever sensitized with repeated isolation, but beta-adrenergic receptor blockade with propranolol (10 or 20 mg/kg) did not affect either of these responses or their sensitization. The high dose of propranolol did, however, reduce vocalizing. These r...

Source: Stress - August 2, 2023 Category: Research Authors: Rachel R Kessler Patricia A Schiml Sean M McGraw Erin N Tomlin Mikayla J Hoeferlin Terrence Deak Michael B Hennessy Source Type: research