Repeated electroconvulsive shock attenuates the depressive-like effects of d-amphetamine withdrawal on brain reward function in rats.
BACKGROUND
The withdrawal of humans from high doses of psychostimulant drugs can result in a transient syndrome which appears isomorphic to endogenous depression. One of the more prominent symptoms is a loss of hedonic capacity; in animals, the anhedonia associated with amphetamine withdrawal has been measured objectively by decrements in responding for intracranial self-stimulation (ICSS).


OBJECTIVE
To date, the effects of amphetamine withdrawal on ICSS responding have been reversed by different antidepressant drugs. In the present study, we sought to reverse withdrawal-induced anhedonia by administration of repeated electroconvulsive shocks (ECS).


METHODS
Rats with electrodes in the lateral hypothalamus were trained on an ascending-series current intensity ICSS paradigm until stable levels of responding were attained. Half of the animals were then administered a 4-day escalating dose schedule of d-amphetamine, and tests for ICSS responding started 12 h after the final injection. During withdrawal, all animals received daily treatment with either ECS or sham-ECS.


RESULTS
Amphetamine withdrawal was associated with reduced ICSS responding; animals treated with ECS exhibited a facilitated recovery compared to sham-ECS treated animals, and returned to control levels of ICSS responding 24 h earlier.


CONCLUSIONS
ECS was able to mitigate the anhedonic effects of d-amphetamine withdrawal, and provides additional support for the use of psychostimulant withdrawal as a model of depression.
Barr
Alasdair M
AM
Department of Psychology, University of British Columbia, Vancouver, Canada.
Zis
Athanasios P
AP
Phillips
Anthony G
AG
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D000697:Central Nervous System Stimulants / Q000009:adverse effects*; D003863:Depression / Q000139:chemically induced* / Q000628:therapy*; D003913:Dextroamphetamine / Q000009:adverse effects*; D004558:Electric Stimulation / Q000379:methods; D004597:Electroshock / Q000379:methods; D008297:Male; D051381:Rats; D020318:Rats, Long-Evans; D012201:Reward; D013375:Substance Withdrawal Syndrome / Q000628:therapy*
D000697:Central Nervous System Stimulants; D003913:Dextroamphetamine