Differential sensitivity to lithium's reversal of amphetamine-induced open-field activity in two inbred strains of mice.
To determine whether genetic differences could contribute to the pharmacological sensitivity of lithium chloride (LiCl) to reverse amphetamine-associated changes in behavior C57BL/6nCrlBR and C3H/HenCrlBR male mice were tested for the ability of an acute dose of LiCl to reverse the locomotor enhancing effects of an acute dose of amphetamine. A series of experiments were conducted that compared dose response of LiCl, chamber lighting conditions, and chamber shape on amphetamine-induced activity in two strains of mice with different genetic backgrounds. Acute amphetamine (3 mg/kg) increased locomotor activity in C57BL/6nCrlBR mice and LiCl (1-4 mEq/kg) blocked this effect. LiCl-induced changes in baseline activity seen at high doses of LiCl were not seen for the low doses. The dark condition reduced time resting but chamber shape did not appear to alter results. In C3H/HenCrlBR mice, amphetamine did not significantly increase levels of activity but did decrease rearing behavior which suggests that genetic difference between C57BL/6nCrlBR and C3H/HenCrlBR mice may contribute to sensitivity to amphetamine. In sum, the ability of LiCl to reverse amphetamine-induced changes in locomotor activity in C57BL/6nCrlBR mice may provide a useful model to study genetic and pharmacological aspects of psychiatric illnesses such as bipolar disorder.
Gould
T J
TJ
CNS Discovery Department, AstraZeneca Pharmaceuticals, 1800 Concord Pike, Wilmington, DE 19850-5437, USA. tgould@astro.temple.edu
Keith
R A
RA
Bhat
R V
RV
D000662:Amphetamines / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D018692:Antimanic Agents / Q000494:pharmacology*; D001714:Bipolar Disorder / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D004195:Disease Models, Animal; D004341:Drug Evaluation / Q000379:methods; D018021:Lithium Chloride / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H / Q000235:genetics / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects*
D000662:Amphetamines; D018692:Antimanic Agents; D000697:Central Nervous System Stimulants; D018021:Lithium Chloride