Haloperidol-Environment Interaction Modulates Expression of c-Fos Proteins in the Basal Ganglia in Rats

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Pezarro Schimmel, Lexy
Haloperidol , Inverse incentive learning , Dopamine , c-Fos immunohistochemistry
Inverse incentive learning is the loss by stimuli of their ability to elicit approach and other responses. This has been shown in the horizontal bar test. Rats in the Paired group (n = 10) were injected with haloperidol (0.25 mg/kg) and initially descended almost immediately but over days descent latencies grew longer. Control rats were tested daily and received haloperidol (Unpaired group, n = 9) or saline (Saline group, n = 10) later in their home cage. Controls showed no evidence of increased descent latencies. On the final test day, all groups were tested after haloperidol and only the Paired group showed increased descent latencies. c-Fos immunohistochemistry was used to identify brain regions associated with inverse incentive learning. Expression of c-Fos positive neurons in the nucleus accumbens core and ventral pallidum was significantly lower in the Paired rats than in the Unpaired and Saline rats, even though all groups received haloperidol on the test day. Compared to the Saline group both the Paired and Unpaired groups showed evidence of lower c-Fos levels in the dorsal striatum and nucleus accumbens shell, possibly a result of daily haloperidol injections. No group differences in c-Fos expression were found in the piriform cortex, ventral hippocampus, ventral tegmental area or lateral habenula. The numbers of rats in the Saline, Paired, and Unpaired groups were: 9, 10, and 6 for the piriform cortex, dorsal striatum, nucleus accumbens and ventral pallidum; 5, 10, and 5 for the ventral hippocampus; 5, 5, and 5 for the ventral tegmental area; and 6, 6, and 7 for the lateral habenula. Results reveal brain region-specific changes in neuronal activity associated with inverse incentive learning. Results support possible underlying neuroplastic changes for learned decreases in responsivity to environmental stimuli.
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