title: Differential effects of serotonin-specific and excitotoxic lesions of OFC on conditioned reinforcer devaluation and extinction in rats.
abstract: The orbitofrontal cortex (OFC) is critical for behavioral adaptation in response to changes in reward value. Here we investigated, in rats, the role of OFC and, specifically, serotonergic neurotransmission within OFC in a reinforcer devaluation task (which measures behavioral flexibility). This task used two visual cues, each predicting one of two foods, with the spatial position (left-right) of the cues above two levers pseudorandomized across trials. An instrumental action (lever press) was required for reinforcer delivery. After training, rats received either excitotoxic OFC lesions made by NMDA (N-methyl-d-aspartic acid), serotonin-specific OFC lesions made by 5,7-DHT (5,7-dihydroxytryptamine), or sham lesions. In sham-lesioned rats, devaluation of one food (by feeding to satiety) significantly decreased responding to the cue associated with that food, when both cues were presented simultaneously during extinction. Both types of OFC lesions disrupted the devaluation effect. In contrast, extinction learning was not affected by serotonin-specific lesions and was only mildly retarded in rats with excitotoxic lesions. Thus, serotonin within OFC is necessary for appropriately adjusting behavior toward cues that predict reward but not for reducing responses in the absence of reward. Our results are the first to demonstrate that serotonin in OFC is necessary for reinforcer devaluation, but not extinction.
authors: Department of Pharmacology and Physiology, Georgetown University Medical Center, Washington, DC 20007, United States. WestE@email.unc.edu
authors: Elizabeth A
authors: EA
authors: West
authors: Patrick A
authors: PA
authors: Forcelli
authors: David L
authors: DL
authors: McCue
authors: Ludise
authors: L
authors: Malkova
mesh_terms: D015116:5,7-Dihydroxytryptamine / Q000633:toxicity; D000704:Analysis of Variance; D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects* / Q000502:physiology; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity*; D005108:Extinction, Psychological / Q000187:drug effects / Q000502:physiology*; D008297:Male; D016202:N-Methylaspartate / Q000633:toxicity; D017397:Prefrontal Cortex / Q000293:injuries* / Q000502:physiology; D051381:Rats; D020318:Rats, Long-Evans; D012054:Reinforcement, Psychology; D018490:Serotonin Agents / Q000633:toxicity*; D018709:Statistics, Nonparametric
chemical_list: D018690:Excitatory Amino Acid Agonists; D018490:Serotonin Agents; D015116:5,7-Dihydroxytryptamine; D016202:N-Methylaspartate