Rats immobilized for 2 hours daily over 7 days developed a heightened behavioral response to a serotonin receptor agonist, 5-MeODMT, measured by forepaw treading and hind-limb abduction. Giving naloxone before each stress session fully blocked this increased reactivity. Conversely, pairing morphine or beta-endorphin with immobilization for 3 days produced an even stronger response than immobilization alone. Chronic immobilization did not affect shaking behavior induced by another serotonin precursor, 5-HTP. These findings suggest chronic stress selectively adapts the 5-HT1 serotonin site and activates an opioid mechanism likely involved in that adaptation.
Injecting gangliosides before repeated restraint stress in rats reversed stress-induced reductions in motor activity and body weight, and enhanced certain behavioral responses linked to serotonin receptors. A single stress session or three days of stress alone did not change the response to a serotonin-receptor drug, but combining gangliosides with three days of stress increased forepaw treading and hindlimb abduction. Gangliosides may speed up adaptive changes in serotonin-1 sites and lessen some aftereffects of stress.