Persistent disruption of overexpectation learning after inactivation of the lateral orbitofrontal cortex in male rats

• Published in: Psychopharmacology Vol. 240; no. 3; pp. 501 - 511
• Main Authors: Lay, Belinda P. P., Choudhury, Ramisha, Esber, Guillem R., Iordanova, Mihaela D.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.03.2023; Springer; Springer Nature B.V
• Subjects: Analysis; Animals; Associative learning; Baclofen; Biomedical and Life Sciences; Biomedicine; Conditioning, Classical - physiology; Cues; Evaluation; Experiments; Extinction behavior; Extinction, Psychological - physiology; Fear; Light; Male; Mice; Muscimol; Muscimol - pharmacology; Neurosciences; Original Investigation; Pharmacology/Toxicology; Prefrontal Cortex; Psychiatry; Psychopharmacology; Rats; Surgery; United States; Learning; Fear; Rat; Extinction; Memory
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-022-06198-2

Rationale and objective Learning to inhibit acquired fear responses is fundamental to adaptive behavior. Two procedures that support such learning are extinction and overexpectation. In extinction, an expected outcome is omitted, whereas in overexpectation two individually trained cues are presented in compound to induce an expectation of a greater outcome than that delivered. Previously, we showed that inactivation of the lateral orbitofrontal cortex (lOFC) in experimentally naïve male rats causes a mild impairment in extinction learning but a profound one in overexpectation. The mild extinction impairment was also transient; that is, it was absent in a cohort of rats that had prior history of inhibitory training (overexpectation, extinction) and their associated controls. This raised the question whether lOFC involvement in overexpectation could likewise be attenuated by prior experience. Methods Using a muscimol/baclofen cocktail, we inactivated the lOFC during overexpectation training in rats with prior associative learning history (extinction, overexpectation, control) and examined its contribution to reducing learned fear. Results Inactivating the lOFC during compound training in overexpectation persistently disrupted fear reduction on test in naïve rats and regardless of prior experience. Additionally, we confirm that silencing the lOFC only resulted in a mild impairment in extinction learning in naïve rats. Conclusion We show that prior associative learning experience did not mitigate the deficit in overexpectation caused by lOFC inactivation. Our findings emphasize the importance of this region for this particular form of fear reduction and broaden our understanding of the conditions in which the lOFC modulates behavioral inhibition.