The ventral pallidum as a critical region for fatty acid amide hydrolase inhibition of nausea-induced conditioned gaping in male Sprague-Dawley rats

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 (CB₁) 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.

Keywords: 2-AG; 2-Arachidonoyl-sn-glycerol; AEA; ANOVA; Analysis of variance; Anandamide; CB(1); CB(2); CTA; Cannabinoid 1; Cannabinoid 2; Conditioned taste avoidance; FAAH; FAAH inhibition; FAEs; Fatty acid amide hydrolase; Fatty acid ethanolamides; IIC; Interoceptive insular cortex; Intraperitoneal; LiCl; Lithium chloride; MAGL; Monoacylglycerol lipase; OEA; Oleoylethanolamide; PEA; PF-3845; PPARα; Palmitoylethanolamide; Peroxisome proliferator-activated receptor alpha; Peroxisome proliferator-activated receptor-α; SAL; SR; SR141716A; Saline; Subcutaneous; TR; Taste reactivity; VEH; VP; Vehicle; Ventral pallidum; i.p.; s.c..