PRE-EXPOSURE ORBITOFRONTAL CORTEX ACTIVATION OR INACTIVATION ON LATENT INHIBITION OF FEAR LEARNING

Latent inhibition (LI) is a phenomenon that presenting a stimulus multiple times without consequences retards subsequent conditioning to that stimulus. LI deficits have been reported in acute schizophrenia patients accompanied by hypoactivation of the orbitofrontal cortex (OFC). Meanwhile, OFC hyperactivation is commonly observed in other psychiatric conditions, including obsessive-compulsive disorder (OCD). Therefore, we examined how differential OFC activation level during tone pre-exposure session of the LI procedure affected the acquisition of cue-induced fear in male Long-Evans rats with freezing as the behavioral readout.
The animals were pre-exposed to daily 45 tones for two consecutive days, followed by fear conditioning on Day 3 (5 tone-shock pairings) and retrieval test on Day 4 (45 tones only). The lateral or medial OFC was activated with NMDA or inactivated with muscimol-baclofen cocktail during the two-day tone pre-exposure. Control groups received saline infusions and were placed into the chambers with or without tone pre-exposure.
Our results showed that animals that underwent two days of tone pre-exposure impaired their conditioned fear to the tones compared to no-exposure controls. For rats with lateral OFC inactivation during pre-exposure, their LI was impaired with freezing levels sit between the pre-exposure and no-exposure controls. Conversely, lateral OFC activation during pre-exposure further enhanced LI. On the other hand, equivalent freezing levels were observed among pre-exposure groups regardless of medial OFC activation level, suggesting intact LI compared to no-exposure controls.
Together, our results suggested that aberrant lateral, but not medial, OFC activation level impaired the processing of irrelevant stimuli in LI.