Original ArticleStimuli Linked to Ethanol Availability Activate Hypothalamic CART and Orexin Neurons in a Reinstatement Model of Relapse
Section snippets
Methods and Materials
Serial forebrain tissue encompassing the PVT and hypothalamic orexin- and CART-containing cell bodies were obtained from rats in which effects of ethanol cue exposure on c-fos expression within the prefrontal cortex, nucleus accumbens, hippocampus, central amygdala, and paraventricular nucleus of the hypothalamus has been reported previously (18). All procedures were carried out in accordance with the NIH Guide for the Care and Use of Laboratory Animals and were approved by the Scripps Research
Results
Rats exposed to the EtOH S+ demonstrated significant reinstatement of responding at the previously active lever. Responding in the presence of the S− remained at extinction levels (for details see ref. 18).
Within the DMH, PF/LHA, and PVN, cytoplasmic CART and nuclear Fos-immunolabeling were rarely, if ever, colocalized. In contrast, within the ARC, significant numbers of cells dual labeled for Fos-protein and CART were observed in both S− and S+-exposed animals. However, in rats exposed to the
Discussion
In this study we show for the first time that arcuate nucleus CART neurons are recruited by EtOH-associated stimuli in a conditioned reinstatement model of relapse. Furthermore, we demonstrate that these stimuli significantly increase the number of Fos-positive hypothalamic orexin neurons, consistent with recent findings of a role for orexin in morphine and cocaine reward seeking (8) and conditioned reinstatement of ethanol seeking in alcohol-preferring (P) rats (12). These findings suggest
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