Reduced Oral Ethanol Avoidance in Mice Lacking Transient Receptor Potential Channel Vanilloid Receptor 1

Abstract

Ethanol is a known oral trigeminal stimulant and recent data indicate that these effects are mediated in part by transient receptor potential channel vanilloid receptor 1 (TRPV1). The importance of this receptor in orally mediated ethanol avoidance is presently unknown. Here, we compared orosensory responding to ethanol in TRPV1-deficient and wild type mice in a brief-access paradigm that assesses orosensory influences by measuring immediate licking responses to small stimulus volumes. TRPV1−/− and control mice were tested with six concentrations of ethanol (3, 5, 10, 15, 25, 40%), capsaicin (0.003, 0.01, 0.03, 0.1, 0.3, 1 mM), sucrose (0.003, 0.01, 0.03, 0.1, 0.3, 1 M), and quinine (0.01, 0.03, 0.1, 0.3, 1, 3 mM) and psychophysical concentration-response functions were generated for each genotype and stimulus. TRPV1 knockouts displayed reduced oral avoidance responses to ethanol regardless of concentration, insensitivity to capsaicin, and little to no difference in sweet or bitter taste responding relative to wild type mice. These data indicate that the TRPV1 channel plays a role in orosensory-mediated ethanol avoidance, but that other receptor mechanisms likely also contribute to aversive oral responses to alcohol.

Fetal ethanol exposure increases ethanol intake by making it smell and taste better

“…Ethanol's trigeminal stimulant effects are partially mediated through the TRPV1 receptor (42). Genetic deletion of the TRPV1 receptor in mice decreases the aversive orosensory responses to ethanol (43). Likewise, repeated transient exposure to ethanol in humans reduces the perception of its oral irritancy (44).…”

Differential neural representation of oral ethanol by central taste-sensitive neurons in ethanol-preferring and genetically heterogeneous rats

“…In rodents, oral ethanol induces concentration-dependent activation of lingual nociceptive neurons in the medullary dorsal horn that receive afferent input from the trigeminal nerve (Carstens et al 1998). Targeted deletion of the transient receptor potential vanilloid type 1 receptor (TRPV1), the sensory receptor for capsaicin expressed on trigeminal nerve endings and activated by ethanol (Caterina et al 1997;Trevisani et al 2002), also reduces ethanol avoidance in mice (Blednov and Harris 2009;Ellingson et al 2009), indicating that trigeminal substrates contribute to oral ethanol aversion. Moreover, psychophysical studies in humans have shown that noxious oral sensations processed by the trigeminal system, such as the "burning" of capsaicin, can be confused with bitter taste (Lim and Green 2007).…”

International Union of Basic and Clinical Pharmacology. LXXVI. Current Progress in the Mammalian TRP Ion Channel Family

“…This may be due to the tonic activation of visceral TRPV1 by nonthermal factors, which suppresses autonomic cold-defense effectors and body temperature; blockade of the activation by TRPV1 antagonists disinhibits thermoeffectors and causes hyperthermia (Romanovsky et al, 2009). In addition to important roles in thermosensation and thermoregulation, TRPV1 has been reported to be important for normal bladder function (Birder et al, 2002), gastrointestinal motility (Rong et al, 2004), behavioral responses to ethanol (Blednov and Harris, 2009;Ellingson et al, 2009), airway inflammation and disease (Geppetti et al, 2006), and detection of salt (Lyall et al, 2004).…”