Strain differences in lithium attenuation of d-Amphetamine-induced hyperlocomotion : A mouse model for the genetics of clinical response to lithium

• Published in: Neuropsychopharmacology (New York, N.Y.) Vol. 32; no. 6; pp. 1321 - 1333
• Main Authors: GOULD, Todd D, O'DONNELL, Kelley C, PICCHINI, Alyssa M, MANJI, Husseini K
• Format: Journal Article
• Language: English
• Published: New York, NY Nature Publishing 01.06.2007; Nature Publishing Group
• Subjects: Adult and adolescent clinical studies; Animals; Antimanic Agents - pharmacokinetics; Antimanic Agents - therapeutic use; Biological and medical sciences; Bipolar disorders; Brain - metabolism; Central Nervous System Stimulants - antagonists & inhibitors; Central Nervous System Stimulants - pharmacology; Data Interpretation, Statistical; Depression; Dextroamphetamine - antagonists & inhibitors; Dextroamphetamine - pharmacology; Dose-Response Relationship, Drug; Hyperkinesis - chemically induced; Hyperkinesis - genetics; Hyperkinesis - prevention & control; Lithium Chloride - pharmacokinetics; Lithium Chloride - therapeutic use; Male; Medical sciences; Mice; Mice, Inbred Strains; Mood disorders; Motor Activity - drug effects; Neuropharmacology; Pharmacology. Drug treatments; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychopharmacology; Species Specificity; Amphetamine derivatives; Mood disorder; Animal model; manic-depressive illness; CNS stimulant; Hyperactivity; Psychotropic; Rodentia; Depression; Lithium; Bipolar disorder; Strain specificity; Endophenotype; Vertebrata; Chemotherapy; Mammalia; stimulant; Mouse; Mood stabilizer; Nootropic agent; Animal; Genetics; Dexamfetamine
• ISSN: 0893-133X; 1740-634X
• DOI: 10.1038/sj.npp.1301254

Lithium attenuation of stimulant-induced hyperlocomotion is a rodent model that may be useful both to understand the mechanism of the therapeutic action of lithium and to develop novel lithium-mimetic compounds. To lay the foundation for future investigations into the neurobiology and genetics of lithium as a therapeutic agent, we studied the effect of lithium on d-amphetamine-induced hyperlocomotion in 12 (3 outbred) mouse strains. In our initial screening, mice received either (1) no drugs, (2) LiCl only, (3) d-amphetamine only, or (4) d-amphetamine and LiCl. Whereas there was no significant effect of LiCl alone on locomotion in any strain, there was a large degree of strain variation in the effects of LiCl combined with d-amphetamine. LiCl attenuated d-amphetamine-induced hyperlocomotion in C57BL/6J, C57BL/6Tac, Black Swiss, and CBA/J mice, whereas CD-1, FVB/NJ, SWR/J, and NIH Swiss mice, which were responsive to d-amphetamine, showed no significant effect of LiCl. d-Amphetamine-induced hyperlocomotion in the C3H/HeJ strain was increased by pretreatment with lithium. A subset of strains were treated for 4 weeks with lithium carbonate before the d-amphetamine challenge, and in each of these strains, lithium produced effects identical to those seen following acute administration. Strain responsiveness to lithium was not dependent upon the dose of either d-amphetamine or LiCl. Further, the results are not explained by brain lithium levels, which suggests that these behavioral responses to lithium are under the control of inherent genetic or other biological mechanisms specific to the effects of lithium on brain function.