Systemic sulpiride in young adult volunteers simulates the profile of cognitive deficits in Parkinson's disease

The role of dopamine (DA) pathways in the pathophysiology of depressive disorder is poorly understood. However, because DA plays a key role in motivational behavior, it is important to study in a disorder characterized by anhedonia, lack of energy and psychomotor retardation. A recently developed dietary manipulation ('tyrosine (TYR) depletion') offers a novel method to assess the role of DA in major depression. We studied 15 euthymic women with a past history of recurrent depression, who received a 74 g amino-acid drink lacking TYR and phenylalanine (PHE) (TYR-free) and a balanced (BAL) amino acid drink on two separate occasions in a double-blind, random-order, crossover design. Plasma prolactin levels rose following the TYR-free drink relative to the balanced mixture, while performance on a spatial recognition memory task was impaired. However, relative to the BAL drink, the TYR-free drink did not lower objective or subjective measures of mood. We conclude that as in healthy volunteers, TYR depletion in euthymic subjects, with a past history of major depression, attenuated DA function, as reflected in increased plasma prolactin levels and decreased spatial memory performance. However ratings of depression were unaffected, suggesting that disruption of dopaminergic function by this manipulation does not induce a lowering of mood in individuals vulnerable to depression.

Section: Discussionsupporting

confidence: 87%

Section: Introductionmentioning

confidence: 99%

Lack of Effect of Tyrosine Depletion on Mood in Recovered Depressed Women

McTavish

Mannie

Harmer

et al. 2005

“…Nicotine effects on response inhibition in this study could also be mediated by enhancement of dopaminergic functioning. The dopaminergic system is believed to modulate a range of cognitive processes, including response inhibition (Brozoski et al, 1979;Mehta et al, 1999;Cropley et al, 2006). Both the striatum (especially the caudate) and prefrontal cortex have been identified as regions important for response inhibition (Lawrence et al, 1998;Volkow et al, 1998Volkow et al, , 2004Aron and Poldrack, 2005;Cropley et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

The Effects of Transdermal Nicotine on Cognition in Nonsmokers with Schizophrenia and Nonpsychiatric Controls

Barr

Culhane

Jubelt

et al. 2007

214

151

Abundant evidence indicates that the neuronal nicotinic acetylcholine receptor (nAChR) system is integral to regulation of attentional processes and is dysregulated in schizophrenia. Nicotinic agonists may have potential for the treatment of cognitive impairment in this disease. This study investigated the effects of transdermal nicotine on attention in individuals with schizophrenia (n ¼ 28) and healthy controls (n ¼ 32). All participants were nonsmokers in order to eliminate confounding effects of nicotine withdrawal and reinstatement that may occur in the study of smokers. Subjects received 14 mg transdermal nicotine and identical placebo in a randomized, placebocontrolled, crossover design. A cognitive battery was conducted before and 3 h after each patch application. The primary outcome measure was performance on the Continuous Performance Test Identical Pairs (CPT-IP) Version. Nicotine significantly improved the performance on the CPT-IP as measured by hit reaction time, hit reaction time standard deviation and random errors in both groups. In addition, nicotine reduced commission errors on the CPT-IP and improved the performance on a Card Stroop task to a greater extent in those with schizophrenia vs controls. In summary, nicotine improved attentional performance in both groups and was associated with greater improvements in inhibition of impulsive responses in subjects with schizophrenia. These results confirm previous findings that a single dose of nicotine improves attention and suggest that nicotine may specifically improve response inhibition in nonsmokers with schizophrenia.

“…Findings in healthy volunteers showed that haloperidol impaired performance in the SWM task (McCartan et al, 2001). Moreover, the D 2 antagonist sulpiride impaired in some (Mehta et al, 1999(Mehta et al, , 2004 but not in all (Mehta et al, 2003(Mehta et al, , 2005) studies working memory performance, while the D 2 receptor agonist bromocriptine enhanced working memory performance in healthy humans (Mehta et al, 2001). In agreement with this finding in humans, systemic administration of the D 2 receptor agonist quinpirole in monkeys influenced working memory performance; while a low dose of quinpirole impaired working memory performance, higher doses led to an enhancement (Arnsten et al, 1995).…”

Section: The Effect Of Haloperidol On Neuropsychological Performancementioning

confidence: 99%

Haloperidol Differentially Modulates Prepulse Inhibition and P50 Suppression in Healthy Humans Stratified for Low and High Gating Levels

Csomor

Stadler

Feldon

et al. 2007

102

Schizophrenia patients exhibit deficits in sensory gating as indexed by reduced prepulse inhibition (PPI) and P50 suppression, which have been linked to psychotic symptom formation and cognitive deficits. Although recent evidence suggests that atypical antipsychotics might be superior over typical antipsychotics in reversing PPI and P50 suppression deficits not only in schizophrenia patients, but also in healthy volunteers exhibiting low levels of PPI, the impact of typical antipsychotics on these gating measures is less clear. To explore the impact of the dopamine D 2 -like receptor system on gating and cognition, the acute effects of haloperidol on PPI, P50 suppression, and cognition were assessed in 26 healthy male volunteers split into subgroups having low vs high PPI or P50 suppression levels using a placebocontrolled within-subject design. Haloperidol failed to increase PPI in subjects exhibiting low levels of PPI, but attenuated PPI in those subjects with high sensorimotor gating levels. Furthermore, haloperidol increased P50 suppression in subjects exhibiting low P50 gating and disrupted P50 suppression in individuals expressing high P50 gating levels. Independently of drug condition, high PPI levels were associated with superior strategy formation and execution times in a subset of cognitive tests. Moreover, haloperidol impaired spatial working memory performance and planning ability. These findings suggest that dopamine D 2 -like receptors are critically involved in the modulation of P50 suppression in healthy volunteers, and to a lesser extent also in PPI among subjects expressing high sensorimotor gating levels. Furthermore, the results suggest a relation between sensorimotor gating and working memory performance.