Lithium Salts
MW of lithium: 6.94 (weighted average of Li6 and Li7 isotopes)
For conditioned taste aversion experiments in rats, we use a "standard" dose of LiCl of 76 mg/kg, administered as 12 ml/kg of 0.15 M LiCl. The rat dose is based on early work of Nachman and Asche 1973 PMID 4697023, who found this to be the minimum dose to induce a maximum CTA (i.e. after 1 pairingof sucrose with 76 mg/kg LiCl, rats showed nearly zero preference for sucrose the next day).
Mice appear somewhat resistant, and require either 20 ml/kg (127 mg/kg) or 40 ml/kg (254 mg/kg) LiCl.
We are also interested in the effects of other lithium salts, in particular lithium carbonate (Li2CO3; LCO) and lithium orotate (LiH3N2O4; LiOr). This table helps convert molarity and dose of lithium of the different salts for equivalent doses of Li:
| Salt | MW | % Li | g/L for 0.15M | dose ml 0.15M/kg | mg salt/kg | mg Li/kg |
|---|---|---|---|---|---|---|
| NaCl | 58.44 | (0.39 Na) | 8.8 | 12 | 105.19 | (41.4 Na) |
| NaOr | 178.08 | (0.13 Na) | 26.71 | 12 | 320.54 | (41.4 Na) |
| LiCl | 42.39 | 0.16 | 6.35 | 12 | 76.30 | 12.5 |
| LiCl | 42.39 | 0.16 | 6.35 | 20 | 127.17 | 41.6 |
| LiCO | 73.89 | 0.19 | 11.08 | 12 | 66.54 | 12.5 |
| LiOr | 162.00 | 0.04 | 24.31 | 12 | 291.79 | 12.5 |
LiOr Preparation
From Pacholko 2023 PMID 37356352: LiOr was synthesized by combining lithium hydroxide (Sigma-Aldrich), and orotic acid (Sigma-Aldrich) in a 1:1 M ratio in distilled water; the NaCl concentration was adjusted to 0.9% and pH to 7.4. Doses were administered as 0.1 ml/10g BW (10 ml/kg), with the highest dose of 15 mg/kg Li+ => 375 mg/kg LiOr => 230 mM (NB: not sure how they got this much to dissolve in water)
orotic acid, Sigma Aldrich O2750-10G ($62.01) CAS 65-86-1, MW 156.10
lithium hydroxide, powder, reagent grade >= 98%, 545856-100G ($45.45) CAS 1310-65-2, MW 23.95
sodium hydroxide, CAS 1310-73-2, MW 40
- Make 500 ml of 0.15M LiOH (1.80 g LiOH / 500ml dH20).
- Make 500 ml of 0.15M NaOH (3.00 g NaOH / 500ml dH20).
- Make 20 ml of 0.15M LiOr by adding 0.47 g orotic acid to 20 ml of 0.15M LiOH, vortex: dissolved after about 2 min of vortexing, store at 4C in foil-wrapped tube.
- Make 20 ml of 0.15M NaOr by adding 0.47 g orotic acid to 20 ml of 0.15M NaOH, vortex: did NOT dissolve -- milky white suspension! Left shaking overnight...
Also from Pacholko 2023: in mice, 100 mg/kg naringin (inhibitor of Organic anion transporting polypeptides
(OATPs) OATP1A2/Oatp1a1/Oatp1a4) and/or 30 mg/kg 6-azauracil (inhibitor of uridine monophosphate synthase (UMPS), which decarboxylases orotic acid) delivered via IP injection (both dissolved in isotonic saline).
Milliequivalents
Clincial literature often refers to milliequivalents (mEq) of lithium salts. A milliequivalent is the millimoles of positive charge, so for monovalent ions like Na+ and Li+, 1 mEq = 1 mmol.
Osmolarity
NaCl and LiCl at low concentrations dissociate almost completely, so 0.15M NaCl or 0.15M LiCl are essentially 0.3 OsM (Citation needed).
LiCO should also dissociate completely (citation needed).
LiOr, however is more tightly bound complex (citation needed). So may need to mix up LiOr in 0.15 NaCl to preserve osmolarity.