Abstract
Background
Amphetamine withdrawal and major depression share many behavioral commonalties in
humans. Therefore, the examination of the behavioral effects of amphetamine withdrawal
in rodents may provide insights into the neurobiological mechanisms underlying both
disorders and aid in the development of animal models of depression that are sensitive
to antidepressant agents.
Methods
We examined the behavioral effects of withdrawal from chronic continuous infusion
of amphetamine (via minipump) in three behavioral paradigms: the intracranial self-stimulation
(ICSS) procedure in rats, the modified forced swim test in rats, and the tail suspension
test in mice.
Results
Amphetamine withdrawal resulted in a prolonged (5 day) deficit in brain reward function
as assessed by elevations in ICSS thresholds. Using a similar regimen of amphetamine
administration, we examined the behavioral effects of withdrawal in a modified rat
forced swim test. Animals that were treated with the highest dose of amphetamine (10
mg/kg/day) exhibited increased climbing behavior and decreased immobility 24 hours
after withdrawal; by the 48-hour testing time point, this effect had dissipated. In
contrast, animals that had been pretreated with 5 mg/kg/day amphetamine exhibited
a pronounced increase in immobility indicative of an increase in “depressive-like”
behavior, coupled with decreases in swimming and climbing. In the mouse tail suspension
test, both regimens of amphetamine pretreatment induced increases in immobility scores,
also indicative of “depressive-like” behavior, 24 hours following withdrawal.
Conclusions
Withdrawal from chronic amphetamine administration results in behavioral changes that
may be analogous to some aspects of depression in humans, such as reward deficits
(i.e., elevations in brain reward thresholds) and behaviors opposite to those seen
after treatment with antidepressant drugs, such as decreased immobility in the forced
swim test and the tail suspension test.
Keywords
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Article info
Publication history
Accepted:
September 4,
2002
Received in revised form:
August 15,
2002
Received:
June 3,
2002
Identification
Copyright
© 2003 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
