Noradrenaline and Dopamine Elevations in the Rat Prefrontal Cortex in Spatial Working Memory

Rossetti, Zvani L.; Carboni, Susanna

doi:10.1523/jneurosci.3038-04.2005

Cited by 91 publications

(66 citation statements)

References 60 publications

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“…In contrast, the present findings and other studies measuring dopamine levels in the terminal fields of the dopaminergic projection report elevations in extracellular dopamine levels persisting above resting levels well after the end of stimulation (Phillips et al, 2004;Rossetti and Carboni, 2005). This suggests that brief, phasic responses of dopaminergic neurons to a stimulus can influence dopamine-dependent neuromodulation in terminal regions well beyond presence of the stimulus.…”

Section: Discussioncontrasting

confidence: 99%

Rule Learning and Reward Contingency Are Associated with Dissociable Patterns of Dopamine Activation in the Rat Prefrontal Cortex, Nucleus Accumbens, and Dorsal Striatum

Stefani¹,

Moghaddam²

2006

J. Neurosci.

124

115

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The midbrain dopamine system has been ascribed roles in reward expectancy, error detection, prediction, and memory. However, these theories typically do not differentiate between dopamine response and action in different forebrain terminal fields. We measured dopamine release in the prefrontal cortex (PFC), nucleus accumbens (NAc), and dorsal striatum (DS) of rats exposed to the same maze apparatus under three behavioral conditions: a set-shift task in which reward depended on discrimination learning and extradimensional set-shifting, a yoked condition in which reward was intermittent and not under the control of the subject, and a "reward-retrieval" variant in which reward was certain on every trial. We found dissociable patterns of dopamine release associated with learning, uncertainty, and reward. Dopamine increased in all three regions when reward was contingent on rule learning and shifting or was uncertain. These increases were sustained after behavior. There was a significant correlation between the magnitude of increase in PFC dopamine and the rapidity with which rats shifted between discrimination rules. In the yoke condition, in which the receipt of reward was always uncertain, the opposite relationship between dopamine levels and likelihood of reward was observed. Predictable, noncontingent reward was associated with increased dopamine levels in the NAc and DS. In contrast, PFC dopamine did not increase significantly above baseline levels. Thus, the dopaminergic projections to the PFC and nucleus accumbens were selectively, yet differentially, activated in situations of uncertainty and cognitive demand, whereas the dopaminergic projection to the DS responded independently of task differences in learning and reward.

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Section: Discussioncontrasting

confidence: 99%

Rule Learning and Reward Contingency Are Associated with Dissociable Patterns of Dopamine Activation in the Rat Prefrontal Cortex, Nucleus Accumbens, and Dorsal Striatum

Stefani¹,

Moghaddam²

2006

J. Neurosci.

124

115

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“…Dopamine efflux in the prefrontal cortex of non-human primates is associated with accuracy in a delayed alternation task [46]. The magnitude of dopamine release in the PFC also predicts memory accuracy in rats [34,38]. In contrast to dopamine, very little is known regarding that correlation between serotonin levels in the prefrontal cortex and working memory.…”

Section: Discussionmentioning

confidence: 99%

Mercury-induced cognitive impairment in metallothionein-1/2 null mice

Eddins

Petro

Pollard

et al. 2008

Neurotoxicology and Teratology

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Metallothioneins are central for the metabolism and detoxification of transition metals. Exposure to mercury during early neurodevelopment is associated with neurocognitive impairment. Given the importance of metallothioneins in mercury detoxification, metallothioneins may be a protective factor against mercury-induced neurocognitive impairment. Deletion of the murine metallothionein-1 and metallothionein-2 genes causes choice accuracy impairments in the 8-arm radial maze. We hypothesize that deletions of metallothioneins genes will make metallothionein-null mice more vulnerable to mercury-induced cognitive impairment. We tested this hypothesis by exposing MT1/MT2-null and wildtype mice to developmental mercury (HgCl 2 ) and evaluated the resultant effects on cognitive performance on the 8-arm radial maze. During the early phase of learning metallothionein-null mice were more susceptible to mercury-induced impairment compared to wildtype. Neurochemical analysis of the frontal cortex revealed that serotonin levels were higher in metallothionein-null mice compared to wildtype mice. This effect was independent of mercury exposure. However, dopamine levels in mercury exposed metallothionein-null mice were lower compared to mercury-exposed wildtype mice. This work shows that deleting metallothioneins increase the vulnerability to developmental mercury-induced neurocognitive impairment. Metallothionein effects on monoamine transmitters may be related to this cognitive effect.

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“…The effect on DA and NE efflux in the HIP were more similar. Increased NE efflux, rather than, or in addition to, DA efflux, may be important for the ability of atypical antipsychotic drugs to improve cognitive function in schizophrenia (Arnsten and Li, 2005;Rossetti and Carboni, 2005). Increases in NE and DA release in the rat mPFC have been reported with 5-HT 1A -receptor agonists (Hajos-Korcsok et al, 1999;Owen and Whitton, 2003); the a 2 -adrenoceptor antagonists RS79948 (Devoto et al, 2004) and 1-(2-pyrimidinyl-piperazine) (Gobert et al, 1999); and the selective 5-HT 2C antagonist, SB242084 .…”

Section: Ne and Serotonin Releasementioning

confidence: 99%

Asenapine Increases Dopamine, Norepinephrine, and Acetylcholine Efflux in the Rat Medial Prefrontal Cortex and Hippocampus

Huang

Dai

et al. 2008

Neuropsychopharmacol

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Atypical antipsychotic drugs, which are more potent direct acting antagonists of brain serotonin (5-HT) 2A than dopamine (DA) D 2 receptors, preferentially enhance DA and acetylcholine (ACh) efflux in the rat medial prefrontal cortex (mPFC) and hippocampus (HIP), compared with the nucleus accumbens (NAc). These effects may contribute to their ability, albeit limited, to improve cognitive function and negative symptoms in patients with schizophrenia. Asenapine (ASE), a new multireceptor antagonist currently in development for the treatment of schizophrenia and bipolar disorder, has complex serotonergic properties based upon relatively high affinity for multiple serotonin (5-HT) receptors, particularly 5-HT 2A and 5-HT 2C receptors. In the current study, the effects of ASE on DA, norepinephrine (NE), 5-HT, ACh, glutamate, and g-aminobutyric acid (GABA) efflux in rat mPFC, HIP, and NAc were investigated with microdialysis in awake, freely moving rats. ASE at 0.05, 0.1, and 0.5 mg/kg (s.c.), but not 0.01 mg/kg, significantly increased DA efflux in the mPFC and HIP. Only the 0.5 mg/kg dose enhanced DA efflux in the NAc. ASE, at 0.1 and 0.5 mg/kg, significantly increased ACh efflux in the mPFC, but only the 0.5 mg/kg dose of ASE increased HIP ACh efflux. ASE did not increase ACh efflux in the NAc at any of the doses tested. The effect of ASE (0.1 mg/kg) on DA and ACh efflux was blocked by pretreatment with WAY100635, a 5-HT 1A antagonist/D 4 agonist, suggesting involvement of indirect 5-HT 1A agonism in both the actions. ASE, at 0.1 mg/kg, increased NE, but not 5-HT, efflux in the mPFC and HIP. ASE, at 0.1 mg/kg (s.c.), had no effect on glutamate and GABA efflux in either the mPFC or NAc. These findings indicate that ASE is similar to clozapine and other atypical antipsychotic drugs in preferentially increasing the efflux of DA, NE, and ACh in the mPFC and HIP compared with the NAC, and suggests that, like these agents, it may also improve cognitive function and negative symptoms in patients with schizophrenia.

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Noradrenaline and Dopamine Elevations in the Rat Prefrontal Cortex in Spatial Working Memory

Cited by 91 publications

References 60 publications

Rule Learning and Reward Contingency Are Associated with Dissociable Patterns of Dopamine Activation in the Rat Prefrontal Cortex, Nucleus Accumbens, and Dorsal Striatum

Rule Learning and Reward Contingency Are Associated with Dissociable Patterns of Dopamine Activation in the Rat Prefrontal Cortex, Nucleus Accumbens, and Dorsal Striatum

Mercury-induced cognitive impairment in metallothionein-1/2 null mice

Asenapine Increases Dopamine, Norepinephrine, and Acetylcholine Efflux in the Rat Medial Prefrontal Cortex and Hippocampus

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