Cognitive and behavioral effects of cholinergic, dopaminergic, and serotonergic blockade in humans

The purpose of this study was to investigate the cognitive and behavioral effects of anticholinergic, antidopaminergic, and antiserotonergic agents given alone and in combination to normal volunteers. Twelve young male volunteers took part in this double-blind randomized, placebo-controlled, crossover study of six drug conditions, each administered on separate days [haloperidol (2 mg PO) ± scopolamine (0.5 mg IV), metergoline (4 mg PO) ± scopolamine (0.5 mg IV), placebo, and scopolamine alone (0.5 mg IV)]. Scopolamine-induced sedation (p <.01), slowed information processing (p <.01 and impaired new learning and memory (p <.02), but did not affect attention or retrieval from semantic memory. Given alone, haloperidol selectively impaired the ability to rapidly switch cognitives sets (p <.05), and metergoline decreased pupil size (p <.01) but did not induce cognitive deficits. In combination with scopolamine, neither haloperidol nor metergoline produced a worsening of the subjects' cognitive performance above and beyond that seen with scopolamine alone. On the contrary, a trend (p <.10) for haloperidol to reverse some of the scopolamine-induced exacerbation of verbal short-term forgetting was observed. The data indicate that scopolamine and haloperidol can independently and selectively affect cognition and that at the doses tested in this study no synergistic exacerbation of cognitive functioning was found when cholinergic blockage was coupled with dopaminergic or serotonergic blockade.