Neuropsychologia 46 (2008) 292–300 Apomorphine effects on episodic memory in young healthy volunteers Alonso Montoya, Samarthji Lal, Matthew Menear, Elisabeth Duplessis, Joseph Thavundayil, Norbert Schmitz, Martin Lepage ∗ Douglas Mental Health University Institute, Department of Psychiatry, McGill University, Canada Received 21 December 2006; received in revised form 13 July 2007; accepted 16 July 2007 Available online 26 July 2007 Abstract Rationale: Dopamine (DA) modulates working memory. However, the relation between DA systems and episodic (declarative) memory is less established. Frontal lobe DA function may be involved. We were interested in assessing whether apomorphine (Apo), a drug used extensively in clinical research as a probe of DA function, has an effect on episodic memory test performance in healthy volunteers. Objective: To investigate the effect of a presynaptic dose of Apo on episodic memory tests and on other tests thought to be sensitive to frontal lobe functions. Methods: Twenty healthy subjects were treated with Apo HCl (5 g/kg sc) or placebo (10 subjects/group) in a randomized, double blind parallel group design and performance on a battery of cognitive tests was assessed. Results: Apomorphine significantly impaired performance on tests of source recognition (d.f. = 19, p = 0.05) and item recognition memory (d.f. = 19, p < 0.05), and memory interference (d.f. = 19, p < 0.010). No significant change was found on other tests (Go/no-Go Test, Categorized Words, Stroop, Trail Making Test, and verbal fluency). Conclusion: Findings in this small sample of subjects suggest that dopaminergic transmission affects episodic memory functions. © 2007 Elsevier Ltd. All rights reserved. Keywords: Episodic memory; Declarative memory; Executive functions; Dopamine; Apomorphine; Prefrontal cortex; Hippocampus; Recall; Recognition 1. Introduction Pharmacological studies in both humans and animals have established a link between working memory functions and dopamine (DA) activity in the brain (Brozoski, Brown, Rosvold, & Goldman, 1979; Fournet, Moreaud, Roulin, Naegele, & Pellat, 2000; Robbins, 2000). Working memory refers to a memory system involved in the temporary maintenance and manipula- tion of information for behavioral purposes (Baddeley, 1992). In healthy humans, the administration of DA receptor ago- nists improves working memory abilities (Luciana & Collins, 1997; Mehta, Swainson, Ogilvie, Sahakian, & Robbins, 2001; Muller, von Cramon, & Pollmann, 1998), whereas, the admin- ∗ Corresponding author at: Douglas Mental Health University Institute, FBC, 6875 boul. LaSalle, Verdun, Quebec H4H 1R3, Canada. E-mail address: Martin.lepage@mcgill.ca (M. Lepage). istration of DA receptor antagonists impairs working memory (Luciana & Collins, 1997; Mehta, Sahakian, McKenna, & Robbins, 1999). The association between DA activity and other memory systems is less clear. Little is known for instance about the role of DA in episodic (declarative) memory, the memory system responsible for the explicit and conscious rec- ollection of events (Tulving, 1983). There is reason to believe that there may be a relationship as many dopamine recep- tors are found in areas of the brain known to be implicated in episodic memory. For instance, DA receptors are found in the prefrontal cortex (Grace, 2002), subcortical regions (cau- date, putamen, thalamus, amygdala) (Gurevich & Joyce, 1999; Schatzberg & Nemeroff, 1995), as well as hippocampal regions (Ryoo & Joyce, 1994). Numerous lesion and neuroimaging studies have shown these same regions to be involved in episodic memory processing (Exner, Weniger, & Irle, 2001; Lepage, Ghaffar, Nyberg, & Tulving, 2000; Rugg, Fletcher, Chua, & Dolan, 1999; Tulving, 2002). Thus, a closer exam- 0028-3932/$ – see front matter © 2007 Elsevier Ltd. All rights reserved. doi:10.1016/j.neuropsychologia.2007.07.012