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.
Aitken R B C (1969) Measurement of feelings using visual analogue rating scales. Proc Roy Soc Med62: 989–997
2.
Arnsten A F T (1997) Catecholamine regulation of the prefrontal cortex. J Psychopharmacol11: 151–162
3.
Arnsten A F T , Goldman-Rakic P S (1986) Reversal of stressinduced delayed response deficits in rhesus monkeys by clonodine and naloxone. Social Neurosci Abst12: 1464–1464
4.
Arnsten A F T , Cai J X, Steere J C, Goldman-Rakic P S (1995) Dopamine D2 receptor mechanisms contribute to age-related cognitive decline: the effects of quinpirole on memory and motor performance in monkeys. J Neurosci15: 3429–3439
5.
Awh E , Jonides J, Smith E E, Schumacher E H, Koeppe R A, Katz S (1996) Dissociation of storage and rehearsal in verbal working memory: evidence from positron emission tomography. Psychol Sci7: 25–31
6.
Baddeley A D (1986) Working memory. Oxford University Press, New York
7.
Baddeley A D , Hitch G J (1974) Working memory. In Bower G H (ed.), Attention and performance, 6th edn, pp. 647–667. Erlbaum, New York
8.
Baker S C , Frith C D, Frackowiak R S J, Dolan R J (1996) Active representation of shape and spatial location in man. Cereb Cortex6: 612–619
9.
Brozoski T J , Brown R M, Rosvold H E, Golman S P (1979) Cognitive deficit caused by regional depletion of dopamine in prefrontal cortex of rhesus monkeys. Science205: 929–932
10.
Castner S A , Williams G V, Goldman-Rakic P S (2000) Reversal of antipsychotic-induced working memory deficits in short-term dopamine D1 receptor stimulation. Science287: 2020–2022
11.
Cohen J (1992) A power primer. Psychol Bul112: 155–159
12.
Cohen J D , Forman S D, Braver T S, Casey B J, Servan-Schreiber D, Noll D C (1994) Activation of prefrontal cortex in a nonspatial working memory task with functional MRI. Hum Brain Map1: 293–304
13.
Cooper J A , Sagar H J, Doherty S M, Jordan N, Tidswell P, Sulivan E V (1992) Different effects of dopaminergic and anticholinergic therapies on cognitive and motor function in Parkinson's disease. Brain115: 1701–1725
14.
D'Esposito M , Detre J A, Alsop D C, Shin R K, Atlas S, Grossman M (1995) The neural basis of the central executive system of working memory. Nature378: 279–281
15.
Duncan G E , Zorn S, Lieberman J A (1999) Mechanisms of typical and atypical antipsychotic drug action in relation to dopamine and NMDA receptor hypofunction hypothesis of schizophrenia. Mol Psychiatry4: 418–428
16.
Ellis K A , Nathan P J (2001) The pharmacology of human working memory. Int J Neuropsychopharmacol4: 299–313
17.
Fletcher P C , Henson R N A (2001) Frontal lobes and human memory: insights from functional neuroimaging. Brain124: 849–881
18.
Fournet N , Moreaud O, Roulin J L, Naegele B, Pellat J (2000) Working memory functioning in medicated Parkinson's disease patients and the effect of withdrawal of dopaminergic medication. Neuropsychology14: 247–225
19.
Funahashi S , Bruce C J, Goldman-Rakic P (1989) Mnemonic coding of visual space in monkey's dorsolateral prefrontal cortex. J Neurophysiol61: 331–349
20.
Furey ML , Petrini P, Haxeby J V (2000) Cholinergic enhancement and increased selectivity of perceptual processing during working memory functions. Science290: 2315–2319
21.
Furey M L , Pietrini P, Haxeby J V, Alexander G E, Lee H C, Van Meter J, Grady C L, Shetty U, Rapoport S I, Schapiro M B, Freo U (1997) Cholinergic stimulation alters performance and taskspecific regional cerebral blood flow during working memory. Proc Natl Acad Sci USA94: 6512–6516
22.
Fuster J M (1997) The prefrontal cortex: anatomy, physiology and neuropsychology of the frontal lobes, 3rd edn.Lippincott-Raven, New York
23.
Gijsman H J , Scarna A, Harmer C J, McTavish S B, Odontiadis J, Cowen P J, Goodwin G M (2002) A dose-finding study on the effects of branch chain amino acids on surrogate markers of brain dopamine function. Psychopharmacology160: 192–197
24.
Goldman-Rakic P S (1988) Topography of cognition: parallel distributed networks in primate association cortexAnnu Rev Neurosci11: 137–156
25.
Goldman-Rakic P S (1990) Cellular and circuit basis of working memory in prefrontal cortex of nonhuman primates. Prog Brain Res85: 325–336
26.
Harmer C J , McTavish S F, Clark L, Goodwin G M, Cowen P J (2001) Tyrosine depletion attenuates dopamine function in healthy volunteers. Psychpharmacology154: 105–111
27.
Jakab R L , Goldman-Rakic P S (1998) 5-Hydroxytryptamine 2A receptors in the primate cerebral cortex: possible site of action of hallucinogenic and antipsychotic drugs in pyramidal cell apical dendrites. Proc Natl Acad Sci USA95: 735–740
28.
Kimberg D Y , D'Esposito M, Farah M J (1997) Effects of bromocriptine on human subjects depend on working memory capacity. Neuroreport8: 3581–3585
29.
Kimberg D Y , Aguirre G K, Lease J, D'Esposito M (2001) Cortical effects of bromocriptine, a D-2 dopamine receptor agonist, in human subjects, revealed by fMRI. Hum Brain Map12: 246–257
30.
Kulisevsky J , Garcia-Sanchez C, Berthier M L, Barbanoj M, Pascual-Sedano B, Gironell A, Estevez-Gonzalez A (2000) Chronic effects of dopaminergic replacement on cognitive function in Parkinson's disease: a two-year follow-up study of previously untreated patients. Mov Disord15: 613–626
31.
Lange K W , Robbins T W, Marsden C D, James M, Owen A M, Paul G M (1992) L-Dopa withdrawal in Parkinson's disease selectively impairs cognitive performance in tests sensetive to frontal lobe dysfunction. Psychopharmacology107: 394–404
32.
Lezak M D (1995) Neuropsychological assessment, 3rd edn.Oxford University Press, New York
33.
Luciana M , Depue R A, Arbisi P, Leon A (1992) Facilitation of working memory in humans by a D2 dopamine receptor agonist. J Cognit Neurosci4: 58–68
34.
Luciana M , Collins P F (1997) Dopaminergic modulation of working memory for spatial but not objects cues in normal humans. J Cognit Neurosci9: 330–347
35.
Luciana M , Collins PF, Depue RA (1998) Opposing roles for dopamine and serotonin in the modulation of human spatial working memory functions. Cereb Cortex8: 218–226
36.
Mehta M A , Sahakian B J, McKenna P J, Robbins T W (1999) Systemic sulpiride in young adult volunteers simulates the profile of cognitive deficits in Parkinson's disease. Psychopharmacology146: 162–174
37.
Mehta M A , Owen A M, Sahakian B J, Mavaddat N, Pickard J D, Robbins T W (2000) Methylphenidiate enhances working memory by modulating discrete frontal and parietal lobe regions in the human brain. J Neurosci20: RC65–RC65
38.
Mehta M A , Swainson R, Ogilvie A D, Sahakian B J, Robbins T W (2001) Improved short-term spatial memory but impaired reversal learning following the dopamine D2 agonist bromocriptine in human volunteers. Psychopharmacology159: 10–20
39.
Muller U , von Cramon D Y, Pollmann S (1998) D1-versus D2-receptor modulation of visuospatial working memory in humans. J Neurosci18: 2720–2728
40.
Nystrom L E , Braver T S, Sabb F W, Delgado M R, Noll D C, Cohen J D (2000) Working memory for letters, shapes, and locations: fMRI evidence against stimulus-based regional organization in human prefrontal cortex. Neuroimage11: 424–446
41.
O'Neill J , Fitten L J, Siembieda D, Halgren E, Kim E, Fisher A, Perryman K (1998) Effects of AF102B and tacrine on delayed match-to-sample in monkeys. Prog Neuro-Psychpharmacol Biol Psychiatry22: 665–678
42.
Owen A M , Stern C E, Look R B, Tracey I, Rosen B R, Petrides M (1998) Functional organization of spatial and nonspatial working memory processing within the human leteral frontal cortex. Proc Natl Acad Sci USA95: 7721–7726
43.
Petrides M (1996) Specialized systems for the processing of mnemonic information within the primate frontal cortex. Philosop Trans Roy Soc London – Series B Biol Sci351: 1455–1461
44.
Ragozzino, M E (2000) The contribution of cholinergic and dopaminergic afferents in the rat prefrontal cortex to learning and memory and attention. Psychobiology28: 238–247
45.
Rao S G , Williams G V, Goldman-Rakic P S (2000) Destruction and creation of spatial tuning by disinhibition: GABAA blockade of prefrontal cortex neurons engaged by working memory. J Neurosci20: 485–494
46.
Sawaguchi T , Goldman-Rakic P S (1991) D1 dopamine receptors in prefrontal cortex: involvement in working memory. Science251: 947–950
47.
Sawaguchi T , Goldman-Rakic P S (1994) The role of D1-dopamine receptors in working memory: local injections of dopamine antagonists into the prefrontal cortex of rhesus monkeys performing an oculomotor delayed-response task. J Neurophysiol71: 515–528
48.
Seemans J K , Durstewitz D, Christie B R, Stevens C F, Sejnowski T J (2001) Dopamine D1/D5 receptor modulation of excitatory synaptic inputs to layer V prefrontal neurons. Proc Natl Acad Sci USA98: 301–306
49.
Shurtleff D , Thoman J R, Schrot J, Kowalski K, Harford R (1994) Tyrosine reveses a cold-induced working memory deficit in humans. Pharmacol Biochem Behav47: 935–941
50.
Ungerleider L G , Haxby J (1984) ‘What’ and ‘where’ in the human brain. Curr Opin Neurobiol4: 157–165
51.
Wechsler D (1974) Wechsler memory scale manual. The Psychological Association, San Antonio TX
52.
Wechsler D (1981) WAIS-R manual. The Psychological Association, New York
53.
Wechsler D (1987) Wechsler Memory Scale revised manual. The Psychological Association, San Antonio TX
54.
Wechsler D (1991) Wechsler Intelligence Scale for Children, 3rd edn.The Psychological Association, San Antonio TX
55.
Williams G V , Goldman-Rakic (1995) Modulation of memory fields by dopamine D1 receptors in prefrontal cortex. Nature376: 572–575
56.
Wilson F A W , Scalaidhe S P O, Goldman-Rakic P (1993) Dissociation of object and spatial processing domains in primate prefrontal cortex. Science260: 1955–1957
