Serotonin and fear retention in the rat

p-Chloroamphetamine (PCA), which releases serotonin (5-HT) stores in brain regions, injected (5 mg/kg, ip) into male rats 40 min prior to the presentation of four inescapable shocks (.065 W) in the right-hand compartment of a normal shuttle box resulted in a profound fear-retention deficit as characterized by the total loss of the freezing and immobility posture that is normally the aftermath of shock presentation; zimelidine (10 mg/kg) 60 min before PCA completely blocked the disruption of fear. The "PCA effect" on fear retention was found at the 2.5 mg/kg but not quite at the 1.25 mg/kg dose, and when PCA (5 mg/kg) had been injected at least 8 hr before conditioning. The selective 5-HT uptake inhibitors zimelidine and fluoxetine, but not the noradrenaline (NA) uptake inhibitor desipramine, blocked the PCA effect, as did the 5-HT antagonist methergoline, but not the selective dopamine antagonist pimozide. A total retention impairment with a conditioning-testing delay of just 60 min was also evidenced, and the administration of PCA up to 2 hr before fear-retention testing also produced the retention deficit; these findings suggest some "retrieval failure." The 5-HT specificity of the PCA effect on fear retention was established by the demonstration that 5-HT-depleted rats (PCA, 2 X 10 mg/kg), but not NA-depleted rats, showed a nearly complete blockade of the fear-retention deficit. These experiments describe a role for 5-HT in both memory storage and retrieval processes.