Haloperidol prevents the consolidation of short-term traumatic memory by modulating interleukin-1β in neural substrates

The role of the dopamine system in modulating traumatic memories in posttraumatic stress disorder (PTSD) is unclear. This study investigated the effect of a dopamine D2 receptor antagonist, haloperidol, on fear responses in rats following a footshock. Fear was assessed by measuring freezing behavior during tests of short-term (STM) and long-term (LTM) memory. All rats were administered haloperidol 45 minutes before a footshock (3mA, 10 seconds) and were subsequently placed in the apparatus for two minutes daily over the next three days without a footshock. In Experiment 1, STM was tested by placing the rats back in the apparatus for a two-minute session. In Experiment 2, LTM was assessed using an identical test, which was repeated seven days later. Experiment 3 utilized the STM protocol, followed by an analysis of brain tissue for the protein interleukin-1b (IL-1b). Results demonstrated that haloperidol reduced freezing behavior in the short-term traumatic memory period. This effect was not observed a week later, indicating that haloperidol did not alter consolidated, long-term fear memories. The footshock was found to alter IL-1b expression in key fear and memory circuits. Importantly, haloperidol’s fear-reducing effect was associated with reduced IL − 1b expression in the nucleus accumbens (NAc), central amygdala (CeA), and hippocampus (CA1, CA2, CA3). These findings suggest that dopamine D2 receptor blockade could represent a new therapeutic approach to preventing the initial consolidation of traumatic memories shortly after an event, but its efficacy in treating established, long-term PTSD may be limited.