1. The ventral pallidum as a critical region for fatty acid amide hydrolase inhibition of nausea-induced conditioned gaping in male Sprague-Dawley rats.
- Author
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Rock EM, Limebeer CL, Aliasi-Sinai L, and Parker LA
- Subjects
- Animals, Butyrates administration & dosage, Infusions, Intraventricular, Lithium Chloride toxicity, Male, Nausea chemically induced, Phenylurea Compounds administration & dosage, Piperidines administration & dosage, Pyridines administration & dosage, Rats, Rats, Sprague-Dawley, Amidohydrolases antagonists & inhibitors, Amidohydrolases metabolism, Basal Forebrain drug effects, Basal Forebrain enzymology, Nausea drug therapy, Nausea enzymology
- Abstract
Here we investigate the involvement of the ventral pallidum (VP) in the anti-nausea effect of fatty acid amide hydrolase (FAAH) inhibition with PF-3845, and examine the pharmacological mechanism of such an effect. We explored the potential of intra-VP PF-3845 to reduce the establishment of lithium chloride (LiCl)-induced conditioned gaping (a model of acute nausea) in male Sprague-Dawley rats. As well, the role of the cannabinoid 1 (CB
1 ) receptors and the peroxisome proliferator-activated receptors-α (PPARα) in the anti-nausea effect of PF-3845 was examined. Finally, the potential of intra-VP GW7647, a PPARα agonist, to reduce acute nausea was also evaluated. Intra-VP PF-3845 dose-dependently reduced acute nausea by a PPARα mechanism (and not a CB1 receptor mechanism). Intra-VP administration of GW7647, similarly attenuated acute nausea. These findings suggest that the anti-nausea action of FAAH inhibition may occur in the VP, and may involve activation of PPARα to suppress acute nausea., (Copyright © 2019. Published by Elsevier Ltd.)- Published
- 2019
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