Acute dopamine depletion with branched chain amino acids decreases auditory top-down event-related potentials in healthy subjects

Abstract

Cerebral dopamine homeostasis has been implicated in a wide range of cognitive processes and is of great pathophysiological importance in schizophrenia. A novel approach to study cognitive effects of dopamine is to deplete its cerebral levels with branched chain amino acids (BCAAs) that acutely lower dopamine precursor amino acid availability. Here, we studied the effects of acute dopamine depletion on early and late attentive cortical processing. Auditory event-related potential (ERP) components N2 and P3 were investigated using high-density electroencephalography in 22 healthy male subjects after receiving BCAAs or placebo in a randomized, double-blind, placebo-controlled crossover design. Total free serum prolactin was also determined as a surrogate marker of cerebral dopamine depletion. Acute dopamine depletion increased free plasma prolactin and significantly reduced prefrontal ERP components N2 and P3. Subcomponent analysis of N2 revealed a significant attenuation of early attentive N2b over prefrontal scalp sites. As a proof of concept, these results strongly suggest that BCAAs are acting on basic information processing. Dopaminergic neurotransmission seems to be involved in auditory top-down processing as indexed by prefrontal N2 and P3 reductions during dopamine depletion. In healthy subjects, intact early cortical top-down processing can be acutely dysregulated by ingestion of BCAAs. We discuss the potential impact of these findings on schizophrenia research.

Acute dopamine and/or serotonin depletion does not modulate mismatch negativity (MMN) in healthy human participants

“…Our finding in N2 was contrary to the attenuated early attentive N2 (i.e. N2b) from a recent DA depletion study, using branch chain amino acids (Neuhaus et al 2009). However, as Neuhaus et al suggested, given that their control or placebo treatment did not contain any amino acids, their findings might have been due to a non-specific effect of amino acid ingestion per se.…”

“…The lack of effect on MMN due to acute DA depletion in the present study is consistent with the finding from our previous study, in which acute D 1 and D 2 receptor stimulation had no effect on MMN . It is also consistent with a recent study where no significant effects on MMN were observed following DA depletion with branch chain amino acids (Neuhaus et al 2009). Further, our ATPD results are consistent with previous evidence that acutely increasing catecholamines (including DA) with methylphenidate (Korostenskaja et al 2008) or acute blockade of D 2 receptors with haloperidol has no effect on MMN Pekkonen et al 2002).…”

Neurocognitive performances of visuospatial attention and the correlations with metabolic and inflammatory biomarkers in adults with obesity

“…the strength of the P3 signals; Neuhaus et al . ), and having fewer striatal dopaminergic receptors is related to obesity (Wang et al . ), the finding that the obese group in the present study showed weaker attentive neural processing (i.e.…”

Go and NoGo: modulation of electrophysiological correlates by female sex steroid hormones

“…It is known that Go and NoGo responses are specifically and differentially modulated by dopamine (Frank et al 2004;Neuhaus et al 2009) and serotonin (Beste et al 2011). Dopamine is proposed to have excitatory effects on the direct or Go pathway, which helps facilitate responding, whereas it is inhibitory on the indirect or NoGo pathway, which suppresses responding (Folstein and Van Petten 2008); serotonin, in turn, contributes to the maintenance of inhibition (Eagle et al 2008).…”