Haloperidol-induced impairment on working memory capacity affecting long term memory performance: the binding hypothesis

The dopaminergic system is implicated in several cognitive processes including memory, attention and executive functions. This study was a double-blind, placebo-randomized trial designed to investigate the effect of dopamine D2 receptor blockade on episodic and working memory and particularly the relationship between executive functions, working memory capacity and long-term memory (LTM). Subjects ingested a single oral dose (4 mg) of haloperidol, a dopamine D2 receptor antagonist or placebo. Multiple linear regression using generalized linear models and a generalized estimating equation were used for statistical analyses. The results demonstrated that haloperidol impaired episodic memory (free recall of words and prose recall), working memory capacity-WMC (operation span task-OSPAN) and highly demanding executive functions (random number generation - RNG). In addition, it demonstrated that despite the large impairment in the RNG task performance in the haloperidol group, it did not affect episodic memory. The OSPAN task is predictive of episodic memory impairment, suggesting that memory impairments produced by haloperidol could be due in part to the impairment of WMC. As WMC partly relies on the appropriate functioning of the medial temporal lobe, probably the haloperidol-induced impairment on episodic memory through the decrease in the performance of WMC may depend on the activation of this area of the brain. The present study is relevant because it provides data on dopaminergic modulation of memory systems; suggesting that the major cause of deficits in episodic memory may be due to hippocampal function and WMC impairments, the latter more specifically with regard to controlled search and binding.