The NMDA receptor partial agonist d-cycloserine does not enhance motor learning

Abstract

Rationale:There has recently been increasing interest in pharmacological manipulations that could potentially enhance exposure-based cognitive behaviour therapy for anxiety disorders. One such medication is the partial NMDA agonist d-cycloserine. It has been suggested that d-cycloserine enhances cognitive behaviour therapy by making learning faster. While animal studies have supported this view of the drug accelerating learning, evidence in human studies has been mixed. We therefore designed an experiment to measure the effects of d-cycloserine on human motor learning.Methods:Fifty-four healthy human volunteers were randomly assigned to a single dose of 250mg d-cycloserine versus placebo in a double-blind design. They then performed a motor sequence learning task.Results:D-cycloserine did not increase the speed of motor learning or the overall amount learnt. However, we noted that participants on d-cycloserine tended to respond more carefully (shifting towards slower, but more correct responses).Conclusion:The results suggest that d-cycloserine does not exert beneficial effects on psychological treatments via mechanisms involved in motor learning. Further studies are needed to clarify the influence on other cognitive mechanisms.

Investigating d-cycloserine as a potential pharmacological enhancer of an emotional bias learning procedure

“…A third potential explanation is that DCS may in fact not have robustly demonstrable effects on emotional learning, or even non-emotional learning (e.g. Butler et al, 2015; Cherry et al, 2014; Günthner et al, 2016). However, there are many (subtle) factors that have to be taken into account when studying the effects of DCS (Hofmann et al, 2015), including factors such as drug dose, timing, and participants’ medication status, or the functional properties of the intervention itself.…”

Glutamatergic regulation of cognition and functional brain connectivity: insights from pharmacological, genetic and translational schizophrenia research

“…In HCs, glycine administration does not improve general cognitive performance on the CogState test battery (Neumeister et al, ) or in a visual attention task (O'Neill et al, ). Furthermore, D‐cycloserine administration does not improve motor sequence learning in HCs (Gunthner et al, ). In contrast, initial studies undertaken in a small sample of 12 HC males support a significant effect of the glycine transporter inhibitor Org 25935 on verbal learning and delayed recall, but not on any of the other cognitive tests employed (D'Souza et al, ).…”

Human perceptual learning is delayed by the N-methyl-D-aspartate receptor partial agonist D-cycloserine

“…While most studies report a positive or null effect of NMDA agonist drugs on learning and cognition (see Introduction), high doses of D-cycloserine have caused impairment visual discrimination performance similar in magnitude to impairments caused by an NMDA-receptor antagonist (Schneider et al, 2000). Our previous work also indicates a worsening of reaction times in a motor task as a function of NMDA receptor agonist activity (Gunthner et al, 2016; see Supplementary Material regarding sensorimotor interaction effects: Sanders et al, 2019). It may be important to consider that different neurocognitive mechanisms could have differing optimal dose ranges.…”

“…Further, we wished to investigate a potential explanation for the large body of research reporting null effects of D-cycloserine on various forms of learning (e.g. procedural learning: Cherry et al, 2014 ; Feld et al, 2013 ; Gunthner et al, 2016 ; reward learning: Scholl et al, 2014 ; declarative memory: Kuriyama et al, 2011 ; working memory: Forsyth et al, 2015 ; fear extinction: Guastella et al, 2007 ; extinction therapies: Kamboj et al, 2011 ; see Hofmann et al, 2013 , 2015 , for review). We suggest that one reason for the apparent mixed success of D-cycloserine may be that D-cycloserine has differential effects on learning and cognition over time.…”