Repeated electroconvulsive shock attenuates the depressive-like effects of d-amphetamine withdrawal on brain reward function in rats

Rationale: 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.