Using monosodium glutamate to initiate ethanol self‐administration in inbred mouse strains

ABSTRACT Voluntary oral ethanol consumption in rodents is generally limited by strong taste‐aversion in these species. Historically, this has been overcome by combining ethanol with a sweetener, typically sucrose or saccharine, and then slowly ‘fading’ away the sweetener. While useful in most instances, this approach has not proven as successful for some inbred strains of mice (e.g. DBA/2J) despite consistent evidence in the literature that these same strains express strong conditioned place preference for intraperitoneal‐ or intragastric‐administered ethanol. Importantly, DBA/2J mice express a polymorphism in a ‘sweet’ taste receptor subunit gene that reduces the potency of sweet substances in these mice. We hypothesized that the presence of this polymorphism might help explain the contrasting behavioral findings of weak voluntary oral ethanol consumption following sucrose‐fade yet robust conditioned place preference for ethanol in this strain. To test this, we compared ethanol consumption initiated by either a ‘traditional’ sucrose‐fade or a fade from an alternative tastant, monosodium glutamate (MSG). We found that in both C57BL/6J and DBA/2J mice, the MSG‐fade produced robust increases in home cage ethanol consumption relative to the traditional sucrose‐fade. This increased ethanol intake following MSG‐fade was evident across a range of ethanol concentrations. Our findings suggest the potential utility of the MSG‐fade to establish stable voluntary oral ethanol consumption in mice, particularly ethanol ‘non‐preferring’ strains such as DBA/2J and lend additional support to the notion that ethanol consumption in DBA/2J mice is limited by pronounced taste aversion.