Anatomical substrates of orexin–dopamine interactions: lateral hypothalamic projections to the ventral tegmental area
Section snippets
Animals and surgery
Adult male Sprague–Dawley rats (Harlan; Birmingham, AL, USA) were kept on a 12 h light–dark cycle and allowed free access to food and water. Experimental procedures were conducted in accord with the National Institutes of Health’s Guide for the Care and Use of Laboratory Animals.
Rats were deeply anesthetized with pentobarbital and glass pipettes (18–24 μm outer diameter) filled with a 3% solution of the retrograde tracer FluoroGold (FG; Fluorochrome, Inc., Englewood, CO, USA) in 0.1 M cacodylic
Retrograde labeling in the LH/PFA
FG injections of the VTA resulted in retrograde labeling that extended from the preoptic regions to the most caudal portions of the LH. The retrogradely-labeled cells in the LH and surrounding nuclei were organized as a dense band of neurons, which extended from the lateral border of the paraventricular hypothalamic nucleus and arched dorsally over the fornix before curving ventrolaterally into the juxtacapsular LH (see Fig. 1). Retrograde labeling was predominantly ipsilateral, but a small
Discussion
Orexin cells contribute to but are not the sole source of a dense projection from the LH to the VTA. The anatomical distributions of orexin and DA suggest that orexin regulates DA neurons via projections from the LH to the VTA and perhaps at the level of the mesocorticolimbic terminal fields.
Acknowledgements
We appreciate the assistance of Tamara Altman in the preparation of figures, and thank Dr. Lothar Jennes for his generous gift of the guinea-pig anti-FluoroGold antibody. This work was supported in part by a NARSAD Young Investigator Award (J.F.), NIH grants MH 45124 and MH 57995 (A.Y.D.), and the National Parkinson Foundation Center of Excellence at Vanderbilt University.
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