Discriminative stimulus properties of lithium chloride in rats

1. Adult male rats were trained to discriminate between an injection of lithium chloride (56 or 75 mg/kg) and saline in a two-lever operant chamber during a 20-minute session. 2. On training days, responding on the designated lever was reinforced under a fixed-ratio 20 (FR 20) schedule of food presentation, whereas responding on the other level had no programmed consequences. 3. Generalization testing with LiCl (10-100 mg/kg) was conducted after each subject reached a criterion of nine of ten sessions where 95% of overall responding occurred on the designated lever, and fewer than twenty responses were made on the other lever before presentation of the first reinforcer. 4. Substituting both lower and higher doses produced decreases in responding on the LiCl-appropriate lever while only higher doses decreased overall response rate. 5. Following generalization tests, animals were divided into two groups and varying doses of LiCl were given in combination with intraperitoneal injections of either dexamethasone (1 and 3.2 mg/kg) or ondansetron (0.32 and 1 mg/kg). 6. At doses that had little or no effect alone, neither ondansetron nor dexamethasone pretreatment blocked the discriminative stimulus properties of LiCl. 7. This research shows that LiCl can act as a highly discriminable stimulus in an operant drug-discrimination paradigm and suggests that the stimulus properties of LiCl do not derive from either direct activation of serotonin type-3 receptors or release of adrenocorticotropic hormone.