Strain differences in the neural, behavioral, and molecular correlates of sweet and salty taste in naive, ethanol- and sucrose-exposed P and NP rats

Abstract

Strain differences between naive, sucrose- and ethanol-exposed alcohol-preferring (P) and alcohol-nonpreferring (NP) rats were investigated in their consumption of ethanol, sucrose, and NaCl; chorda tympani (CT) nerve responses to sweet and salty stimuli; and gene expression in the anterior tongue of T1R3 and TRPV1/TRPV1t. Preference for 5% ethanol and 10% sucrose, CT responses to sweet stimuli, and T1R3 expression were greater in naive P rats than NP rats. The enhancement of the CT response to 0.5 M sucrose in the presence of varying ethanol concentrations (0.5-40%) in naive P rats was higher and shifted to lower ethanol concentrations than NP rats. Chronic ingestion of 5% sucrose or 5% ethanol decreased T1R3 mRNA in NP and P rats. Naive P rats also demonstrated bigger CT responses to NaCl+benzamil and greater TRPV1/TRPV1t expression. TRPV1t agonists produced biphasic effects on NaCl+benzamil CT responses, enhancing the response at low concentrations and inhibiting it at high concentrations. The concentration of a TRPV1/TRPV1t agonist (Maillard reacted peptides conjugated with galacturonic acid) that produced a maximum enhancement in the NaCl+benzamil CT response induced a decrease in NaCl intake and preference in P rats. In naive P rats and NP rats exposed to 5% ethanol in a no-choice paradigm, the biphasic TRPV1t agonist vs. NaCl+benzamil CT response profiles were higher and shifted to lower agonist concentrations than in naive NP rats. TRPV1/TRPV1t mRNA expression increased in NP rats but not in P rats exposed to 5% ethanol in a no-choice paradigm. We conclude that P and NP rats differ in T1R3 and TRPV1/TRPV1t expression and neural and behavioral responses to sweet and salty stimuli and to chronic sucrose and ethanol exposure.

TRPM5-dependent amiloride- and benzamil-insensitive NaCl chorda tympani taste nerve response

“…As stated above, the differences between our results and the findings reported by Smith et al (45) may be related to significant differences in the methods used in the two studies. In our studies, putative TRPV1/ TRPV1t agonists and antagonists show similar effects in WT mice, PLC␤ 2 KO mice, Sprague-Dawley rats, P rats, and NP rats (6). The nonpungent agonists of TRPV1/TRPV1t-dependent Bz-insensitive NaCl CT responses modulate human salt taste in a biphasic manner (11,20).…”

“…1). Unlike WT mice, TRPV1 KO mice did not respond to RTX, ethanol, GalA-MRPs, and nicotine with an increase in the CT response above the baseline rinse level (6). However, in another study, CT responses to a concentration series of NaCl with and without amiloride did not differ between the two genotypes (45).…”

“…1), Sprague-Dawley rats, alcohol-preferring (P) rats, and alcohol-non-preferring (NP) rats (6,26). In addition, several low-affinity blockers that inhibit the Bz-insensitive NaCl CT response in the micromolarto-millimolar range include RTX, capsaicin, cetylpyridinium chloride, Maillard reacted peptides (MRPs), N-geranylcyclopropylcarboximide, ethanol, and nicotine (6,11,20,26,27,29,30,40,41,48). Our whole nerve data are supported by the effect of TRPV1 agonists on single CT nerve fibers.…”

A Genetic Animal Model of Alcoholism for Screening Medications to Treat Addiction

“…Genetic animal models of alcoholism, the P rat in this case, engaging in binge-like drinking, which results in BACs of 80 mg% and higher (c.f., Bell et al, 2011, 2014), display numerous changes in glutamate receptor and/or subunits, transporters, scaffolding proteins as well as other associated gene expression levels in discrete brain regions of the mesocorticolimbic and extended amygdala circuits (Bell et al, 2016; Bell, Kimpel, et al, 2009; Coleman et al, 2011; McBride, Kimpel, et al, 2014; McBride et al, 2009, 2010; McBride, Rodd, et al, 2014; McClintick et al, 2015; Rodd et al, 2008). These changes in glutamatergic neurotransmission include enhanced receptor activation and intracellular downstream signaling cascades (Cozzoli et al, 2009; Szumlinski et al, 2007; Tabakoff et al, 2009).…”

Oral Nicotine Self-Administration in Rodents

“…A convincing literature indicates that common genetic factors influence sensitivity to sweet taste and oral alcohol intake in inbred mouse strains [89] and congenic strains [90]. Rat stains selectively bred for alcohol preference also show higher preference for sucrose and saccharin when compared to controls [91, 92]. These findings, coupled with the finding that many mouse strains show an increase in alcohol intake (dose) and preference ratios when saccharin is added to both drinking fluids in a 2-bottle choice [50], provides compelling data that support the assertion that sweet taste factors play an important role in regulating oral alcohol intake.…”