DBA/2J mice develop stronger lithium chloride-induced conditioned taste and place aversions than C57BL/6J mice

Genetic differences in lithium-induced conditioned aversion were examined using both place- and taste-conditioning procedures. In the place-conditioning procedure, adult male C57BL/6J (B6) and DBA/2J (D2) mice were exposed to a differential conditioning procedure in which each mouse received four 30-min pairings of a distinctive floor cue immediately after IP injections of either 0.75, 1.5, or 3. 0 mEq/kg LiCl. A different floor cue was paired with saline injections. A separate group of control mice received saline injections paired with both floor types. Subsequent floor preference testing revealed greater conditioned aversion in D2 mice compared to B6 mice in groups receiving 3.0 mEq/kg LiCl. Lower LiCl doses did not produce conditioning in either strain. In a conditioned taste-aversion procedure, fluid-restricted mice received four trials in which access to 0.2 M NaCl solution was followed by IP injection of either 0.75, 1.5, 3.0, or 6.0 mEq/kg LiCl. D2 mice showed stronger conditioned taste aversion than B6 mice at all doses, suggesting that taste conditioning may be a more sensitive index of aversive drug sensitivity than place conditioning. These findings are not well explained by strain differences in general learning ability or by strain differences in stimulus salience or innate preference. Rather, these data appear more consistent with previous studies showing strain differences in lithium pharmacokinetics and in general sensitivity to aversive events.