The modulatory effects of dopamine D1 and D2 receptor function on object working memory in humans

Abstract

The role of dopamine D1 and D2 receptors in modulating object working memory in humans is poorly understood. The current study was designed to investigate the effects of D1 and D2 receptor modulation on object working memory. Twelve healthy subjects underwent testing under three conditions (0.05 mg pergolide (D1/D2 receptor agonist), 2.5 mg bromocriptine (D2 receptor agonist) and placebo] in a double-blind, placebo-controlled repeated measures design. Subjects performed the object working memory N-back task pre-drug and 1.5 h and 3 h post-drug administration. Neither pergolide nor bromocriptine had an effect on object working memory performance. These findings suggest that object working memory may not be modulated by D1 and D2 receptors in humans.

Tonic Dopaminergic Stimulation Impairs Associative Learning in Healthy Subjects

“…The dose of 0.1 mg per day was selected based on prior studies showing positive effects of a single dose of pergolide on cognition (Kimberg and D'Esposito, 2003;Muller et al, 1998). A third study using a lower dose (0.05 mg) had no effect on cognitive performance (Bartholomeusz et al, 2003). The PLACEBO group (n ¼ 20, five females) received a standard placebo substance (99.5% mannitol, 0.5% erosil) in identical capsules.…”

“…Results for the mixed D1/D2-like receptor dopamine agonist pergolide are inconsistent as well: pergolide improved working memory in one study (Muller et al, 1998), was effective only in a subgroup of the studied sample (Kimberg and D'Esposito, 2003), or proved ineffective (Bartholomeusz et al, 2003;Roesch-Ely et al, 2005). Even under conditions of endogenous dopamine depletion via tyrosine/phenylalanine depletion, a deterioration of working memory performance was observed after pergolide administration (Ellis et al, 2005).…”

“…However, research in healthy humans has so far failed to clearly elucidate the effects of dopamine agonist administration on cognitive performance (Ellis et al, 2005). Some studies with the selective D2-like receptor agonist bromocriptine yielded positive results on memory performance (Luciana et al, 1998;Mehta et al, 2001), whereas others failed to find an effect (Bartholomeusz et al, 2003;Kimberg et al, 1997;Muller et al, 1998) or even reported negative effects on cognition (Gibbs and D'Esposito, 2005). Considering the predominance of D1-like dopamine receptors in learningcritical structures like the hippocampus and the prefrontal cortex, one would expect a greater potential of D1-like receptor agonists in learning modulation (Jay, 2003).…”

Boosting Focally-Induced Brain Plasticity by Dopamine

“…These are consequently affected in diseases with disturbed DA function such as Parkinson's syndrome or schizophrenia (Grace et al 1998). DAergic modulation on cognitive functions has long been investigated intensively, and the results at first glance revealed that DA-enhancing agents facilitated working and long-term memory, whereas DA receptor blockers impaired it (Luciana et al 1992;Kimberg et al 1997;Luciana and Collins 1997;Muller et al 1998;Mehta et al 1999Mehta et al , 2001Bartholomeusz et al 2003;Knecht et al 2004;Floel et al 2005). However, the DAergic influence on cognition might be not quite as simple as originally thought: It might depend on dosage, DAergic subreceptor specificity, and task characteristics (Kulisevsky 2000;Floresco and Phillips 2001).…”

“…Such a focusing mechanism is particularly necessary for consolidation of cognitive functions related to learning and memory, which require long-term stabilization of one or a set of limited representations and suppression of other nonsignificant inputs in neural networks. Several studies have suggested the importance of DAergic focusing on cognition in humans (Kimberg et al 1997;Muller et al 1998;Mehta et al 1999;Bartholomeusz et al 2003;Knecht et al 2004;Floel et al 2005), but direct neurophysiological evidence for such a focusing action of DA in humans is still missing.…”