Eugene R. Delay

The Taste of Monosodium Glutamate: Membrane Receptors in Taste Buds

Receptor proteins for photoreception have been studied for several decades. More recently, putative receptors for olfaction have been isolated and characterized. In contrast, no receptors for taste have been identified yet by molecular cloning. This report describes experiments aimed at identifying a receptor responsible for the taste of monosodium glutamate (MSG). Using reverse transcriptase (RT)-PCR, we found that several ionotropic glutamate receptors are present in rat lingual tissues. However, these receptors also could be detected in lingual tissue devoid of taste buds. On the other hand, RT-PCR and RNase protection assays indicated that a G-protein-coupled metabotropic glutamate receptor, mGluR4, also is expressed in lingual tissues and is limited only to taste buds. In situ hybridization demonstrated that mGluR4 is detectable in 40–70% of vallate and foliate taste buds but not in surrounding nonsensory epithelium, confirming the localization of this metabotropic receptor to gustatory cells. Expression of mGluR4 in taste buds is higher in preweaning rats compared with adult rats. This may correspond to the known higher sensitivity to the taste of MSG in juvenile rodents. Finally, behavioral studies have indicated that MSG andl-2-amino-4-phosphonobutyrate (l-AP4), a ligand for mGluR4, elicit similar tastes in rats. We conclude that mGluR4 may be a chemosensory receptor responsible, in part, for the taste of MSG.

Endogenous cannabinoids as an aversive or counter-rewarding system in the rat

Human use of marijuana (Cannabis sativa) is widely assumed to have rewarding properties, a notion supported by its widespread recreational use. However, no study has clearly demonstrated such effects in animal models. The purpose of this study was to test for the presumed rewarding effect of cannabinoids using a conditioned place preference paradigm. The results showed that animals failed to develop place conditioning at a low dose (1.5 mg/kg) and developed a place aversion at a high dose (15 mg/kg) of the active principle in marijuana, delta 9-tetrahydrocannabinol (delta 9-THC), a finding consistent with most previous studies. Moreover, the administration of the cannabinoid antagonist SR141716A induced a conditioned place preference at both a low (0.5 mg/kg) and a high (5 mg/kg) dose. In summary, cannabinoid antagonism produced place preference while cannabinoid agonism induced place aversion. These results suggest that endogenous cannabinoids serve normally to suppress reward or to induce aversion.

Sucrose threshold variation during the menstrual cycle

Sucrose thresholds were measured at three points during the menstrual cycle for 14 women who were not taking oral contraceptives. Thirteen men also were tested at similar intervals. Sucrose thresholds of the men remained constant throughout the experiment. During menstruation and postovulation, the thresholds of the women were similar to the thresholds of the men, whereas during preovulation the thresholds of the women are significantly lower. The stable sucrose thresholds of the men suggest that ovarian hormones may be involved in the variation in sucrose sucrose thresholds of the women. The increase in sensitivity of the women during preovulation may have been related to the high level of estrogen, whereas the decrease in sensitivity during postovulation may be due to some type of interaction between estrogen and progesterone.

Time Estimation in Humans: Effects of Ambient Illumination and Sex:

7 male and 7 female college students made estimations of 15-sec. intervals in conditions of dark, low and high ambient illumination. Analysis of variance showed significant effects of illumination and illumination by sex. Increased light levels shortened time estimation except for males under high light intensity. Results are discussed in terms of arousal theory and the relevance of these factors in research on time estimation.

Double P2X2/P2X3 Purinergic Receptor Knockout Mice Do Not Taste NaCl or the Artificial Sweetener SC45647

The P2X ionotropic purinergic receptors, P2X2 and P2X3, are essential for transmission of taste information from taste buds to the gustatory nerves. Mice lacking both P2X2 and P2X3 purinergic receptors (P2X2/P2X3(Dbl-/-)) exhibit no taste-evoked activity in the chorda tympani and glossopharyngeal nerves when stimulated with taste stimuli from any of the 5 classical taste quality groups (salt, sweet, sour, bitter, and umami) nor do the mice show taste preferences for sweet or umami, or avoidance of bitter substances (Finger et al. 2005. ATP signaling is crucial for communication from taste buds to gustatory nerves. Science. 310[5753]:1495-1499). Here, we compare the ability of P2X2/P2X3(Dbl-/-) mice and P2X2/P2X3(Dbl+/+) wild-type (WT) mice to detect NaCl in brief-access tests and conditioned aversion paradigms. Brief-access testing with NaCl revealed that whereas WT mice decrease licking at 300 mM and above, the P2X2/P2X3(Dbl-/-) mice do not show any change in lick rates. In conditioned aversion tests, P2X2/P2X3(Dbl-/-) mice did not develop a learned aversion to NaCl or the artificial sweetener SC45647, both of which are easily avoided by conditioned WT mice. The inability of P2X2/P2X3(Dbl-/-) mice to show avoidance of these taste stimuli was not due to an inability to learn the task because both WT and P2X2/P2X3(Dbl-/-) mice learned to avoid a combination of SC45647 and amyl acetate (an odor cue). These data suggest that P2X2/P2X3(Dbl-/-) mice are unable to respond to NaCl or SC45647 as taste stimuli, mirroring the lack of gustatory nerve responses to these substances.

Effects of illumination on activity following superior colliculus and caudate lesions in young and older rats

Abstract Illumination dependent hyperactivity following lesions of the superior colliculus and the head of the caudate nucleus, separately and in combination, was studied in young and older rats tested in the light and dark. While control animals of both age groups exhibited an illumination effect, there were age related differences in the pattern of locomotor activity during the test session as well as over days that interacted with illumination level. None of the lesions appeared to alter activity in the young animals. In the older animals, separate lesions of the superior colliculus and the head of caudate produced hyperactivity in the light but not in the dark, which showed a recovery of function. Simultaneously lesioning these structures eliminated the light-dark effect immediately after surgery and delayed recovery of function. These results support the notion of a functional system regulating illumination dependent activity.

Age and arousal in the rat

The influence of illumination level on locomotor activity and reaction times of three age groups (25, 90, and 180 days old) of rats was studied. Age-related differences were obtained, and consistent effects on the two behavioral measures were obtained for the individual animals.

Behavioral responses to glutamate receptor agonists and antagonists implicate the involvement of brain-expressed mGluR4 and mGluR1 in taste transduction for umami in mice

Recent molecular studies have identified many candidate receptors for umami, typically the taste of monosodium glutamate (MSG). The candidate receptors, including taste-mGluR4, T1R1+T1R3, and truncated mGluR1, respond to MSG in the millimolar concentration range. Expression of brain-expressed mGluR4 and mGluR1 with much higher sensitivities to glutamate has also been reported in taste papillae. To test the involvement of brain-expressed mGluRs in umami taste, we tested glutamate agonists and antagonists at concentration ranges relevant to both types of the receptors using a combination of a detection threshold and conditioned taste aversion (CTA) methods in mice. The detection threshold experiment showed that mice could detect the group III mGluR agonist L(+)-2-amino-4-phosphonobutyrate (L-AP4) taste thresholds at 0.0009-0.0019 mM. Mice conditioned using CTA methods to avoid either MSG or MPG showed aversive responses to MSG with and without amiloride or to MPG, respectively, at concentrations of 0.0001 mM and above. A CTA to L-AP4 or MSG showed comparable concentration-response ranges for L-AP4 and MSG. The Group III mGluR antagonist, (RS)-α-cyclopropyl-4-phosphonophenylglycine (CPPG), and the mGluR1 antagonist, 1-aminoindan-1,5-dicarboxylic acid (AIDA), suppressed aversive responses to glutamate agonists at concentrations between 0.0001 and 100mM in the CTA experiments. Our results suggest the possibility that brain-expressed mGluR4 and mGluR1 may contribute to umami taste in mice.

Effects of Ambient Noise on Time Estimation by Humans

10 male and 10 female undergraduates were asked to estimate 5-, 10-, 15-, and 30-sec. intervals under five intensities of ambient noise (50, 60, 70, 80, and 90 dB). Interval estimates became shorter as the intensity of noise increased from 50 to 80 dB but became longer at 90 dB. The effects of intensity of noise were most prominant in the two longest intervals. These results are interpreted in terms of CNS arousal theory.

Comparison of l-monosodium glutamate and l-amino acid taste in rats

T1R2/T1R3 heterodimers are selectively responsive to sweet substances whereas T1R1/T1R3 receptors are selective for umami substances, represented by monosodium glutamate (MSG), and for L-amino acids. If a single receptor is responsible for detection of umami and L-amino acids, then it would be predicted that MSG and L-amino acids elicit similar tastes in rats. The present study compared the taste profile of MSG with four amino acids (glycine, L-proline, L-serine and L-arginine) using conditioned taste aversion, detection threshold, and taste discrimination methods. These experiments were designed to either reduce or neutralize the taste of sodium associated with MSG and the other amino acids. Detection threshold studies showed that rats were most sensitive to L-arginine and least sensitive to L-proline. Glycine and L-serine thresholds were similar to those previously reported for MSG. Like MSG, a conditioned taste aversion to each of the four amino acids generalized to sucrose in the presence of amiloride, a sodium channel blocker. Rats showed moderate generalization of aversion between MSG and L-arginine, suggesting that these two amino acids taste only moderately alike. However, the taste aversion experiments indicated that glycine, L-serine, and L-proline elicit taste sensations similar to MSG when amiloride is present. Discrimination experiments further compared the tastes of these three amino acids with MSG. When the sodium taste associated with MSG was reduced or neutralized, glycine and L-proline elicited tastes very similar but not identical to the taste of MSG. Low (but not higher) concentrations of L-serine were also difficult for rats to discriminate from MSG. While there are taste qualities common to all of these amino acids, the perceptual differences found in this study, combined with previous reports, suggest either multiple taste receptors and/or multiple signaling pathways may be involved in umami and amino acid taste perception in rats.