Mesocortical dopamine modulation of executive functions: beyond working memory

Floresco, Stan; Magyar, Orsolya

doi:10.1007/s00213-006-0404-5

Cited by 351 publications

(266 citation statements)

References 120 publications

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“…Animals exposed to prenatal cocaine also exhibit cocaine-induced deficits in sustained and selective attention, short term memory and increased reactivity to stress (Romano and Harvey, 1996;Garavan et al, 2000;Morgan et al, 2002;Morrow et al, 2002;Gabriel et al, 2003;Gendle et al, 2003;Thompson et al, 2005). As catecholamine neurotransmission has a critical influence on PFC function (Coull, 1994;Murphy et al, 1996;Dalley et al, 2004;Seamans and Yang, 2004;Arnsten and Li, 2005;Floresco and Magyar, 2006) it is reasonable to suspect that the impact of prenatal cocaine on these developing transmitter systems may contribute to the behavioral abnormalities described above.…”

mentioning

confidence: 99%

Prenatal cocaine exposure enhances responsivity of locus coeruleus norepinephrine neurons: Role of autoreceptors

et al. 2007

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Children exposed to cocaine during gestation have a higher incidence of neurobehavioral deficits. The neurochemical bases of these deficits have not been determined, but the pharmacology of cocaine and the nature of the abnormalities suggest that disruptions in catecholaminergic systems may be involved. In the current study, we used a rat model of prenatal cocaine exposure to examine the impact that this exposure has on the locus coeruleus (LC) noradrenergic system in offspring. Pregnant rats received twice-daily intravenous injections of cocaine (3 mg/kg) or saline between gestational days 10 and 20, and progeny were tested as juveniles. Exposure to a mild stressor elevated an index of norepinephrine turnover in the prefrontal cortex and also increased Fos expression in tyrosine hydroxylase-positive LC neurons in rats exposed to prenatal cocaine but not in rats exposed to prenatal saline. No change in the number of tyrosine hydroxylase-positive neurons in the LC was observed between the two prenatal treatment groups. Specific binding of [ 125 I]-para-iodoclonidine, a radioligand with specificity for high affinity α2A-adrenergic receptors, was decreased in the LC of rats exposed to prenatal cocaine compared to prenatal saline controls. As α 2 -adrenergic receptors on LC norepinephrine neurons function as autoreceptors, their down-regulation by prenatal cocaine exposure provides a plausible mechanism for the observed heightened reactivity of norepinephrine neurons in these animals. These data indicate that prenatal cocaine exposure results in lasting changes to the regulation and responsivity of rat LC norepinephrine neurons. A similar dysregulation of LC norepinephrine neurons may occur in children exposed to cocaine during gestation, and this may explain, at least partly, the increased incidence of cognitive deficits that have been observed in these subjects.

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confidence: 99%

Prenatal cocaine exposure enhances responsivity of locus coeruleus norepinephrine neurons: Role of autoreceptors

et al. 2007

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“…Blockade of prefrontal D 1 receptors impaired set-shifting (Ragozzino, 2002) whereas infusions of D 1 agonists were without effect (Fletcher et al, 2005;Floresco et al, 2006b). This is in contrast to the effects of mesocortical D 1 receptor manipulations on working memory, with D 1 receptor blockade impairing performance and stimulation of these receptors either impairing or improving working memory, dependent on a number of factors (reviewed in Floresco and Magyar, 2006). Taken together, these data indicate that although physiological levels of D 1 receptor tone facilitate efficient shifts between strategies, pharmacological augmentation of D 1 activity beyond normal levels does not appear to provide any additional beneficial effect to these processes.…”

Section: Excessive D 2 But Not D 1 Receptor Activation Induces Fumentioning

confidence: 99%

Ventral Striatal Dopamine Modulation of Different Forms of Behavioral Flexibility

Haluk

Floresco

2009

Neuropsychopharmacol

184

174

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Different forms of behavioral flexibility are facilitated by interactions between separate regions of the prefrontal cortex and their striatal outputs. However, the contribution of ventral striatal dopamine (DA) to these functions is unclear. The present study assessed the involvement of DA receptors in the nucleus accumbens (NAc) core on either between-or within-strategy shifts using operant chamberbased tasks. Strategy set-shifting required rats initially to learn a visual-cue discrimination and, on the following day, shift to using an egocentric spatial response strategy to obtain reward. For reversal learning, rats were initially trained on a response discrimination and then required to select the opposite lever to receive food reward. Intra-NAc microinfusions of D 1 (SCH23390) but not D 2 (eticlopride) receptor antagonists impaired set-shifting, disrupting the maintenance of a new strategy. Conversely, supranormal activation of D 2 (quinpirole) but not D 1 (SKF81297) receptors also impaired set-shifting, inducing perseverative deficits. However, only infusions of the D 2 agonist impaired reversal learning, but did so without disrupting initial response learning. Thus, mesoaccumbens DA, acting on D 1 receptors, selectively facilitates complex forms of flexibility requiring shifts between different strategies, but does not appear to contribute to simpler forms of flexibility entailing shifts of specific stimulus-reward associations. In contrast, abnormal increases in D 2 receptor activity cause a more general impairment in behavioral flexibility. These findings suggest that deficits in these forms of executive functioning observed in disorders linked to dysfunction of the DA system may be attributable in part to aberrant increases or decreases in mesoaccumbens DA activity.

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“…For example, very low and very high physiological levels of adrenal steroids are associated with increased cell death in the hippocampus, whereas intermediate levels are associated with decreased cell death (Joels, 2007). In addition, dopamine activation of the D1 receptor in the prefrontal cortex mediates working memory performance with an inverted U-shape (Floresco and Magyar, 2006). Furthermore, physiologically low and pharmacologically high levels of 17b-estradiol and estrone increase hippocampal cell proliferation, whereas medium levels do not have an effect (Barha et al, 2009).…”

Section: Different Forms Of Estradiol Influence Hippocampusdependent mentioning

confidence: 99%

Low Doses of 17α-Estradiol and 17β-Estradiol Facilitate, Whereas Higher Doses of Estrone and 17α- and 17β-Estradiol Impair, Contextual Fear Conditioning in Adult Female Rats

Barha

Dalton

Galea

2009

Neuropsychopharmacol

108

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Estrogens are known to exert significant structural and functional effects in the hippocampus of adult rodents. In particular, 17b-estradiol can improve, impair, or have no effect on hippocampus-dependent learning and memory depending on dose and time of administration. The effects of other forms of estrogen, such as estrone and 17a-estradiol, on hippocampus-dependent learning have not been as thoroughly investigated. Therefore, the purpose of this study was to investigate the effects of 17b-estradiol, estrone, and 17a-estradiol at three different doses on two different tasks: hippocampus-dependent contextual fear conditioning and hippocampusindependent cued fear conditioning. Adult ovariectomized female rats were injected with one of the estrogens at one of the three doses 30 mins before conditioning to assess the rapid effects of these estrogens on acquisition. Twenty-four hours later memory for the context was examined and 1 h later memory for the cue (tone) was assessed. Levels of synaptophysin were examined in the dorsal hippocampus of rats to identify a potential synaptic correlate of hormonal effects on contextual fear conditioning. Low 17b-estradiol and 17a-estradiol enhanced, whereas high 17b-estradiol and 17a-estradiol impaired, contextual fear conditioning. Only the middle dose of estrone severely impaired contextual fear conditioning. Estrogens did not alter performance in the hippocampus-independent cued task. Synaptophysin expression was increased by estrone (at a middle and high dose) and 17b-estradiol (at a middle dose) in the CA3 region of the hippocampus and was not correlated with cognition. The results of this study indicate that estradiol can positively or negatively influence hippocampus-dependent learning and memory, whereas estrone impairs hippocampus-dependent learning and memory in a dose-dependent manner. These results have important therapeutic implications, as estrone, a main component of a widely used hormone replacement therapy, was shown to have either a negative effect or no effect on learning and memory. It may be possible to use 17a-estradiol and lower doses of estrogens as potential alternatives in hormone replacement therapies.

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Mesocortical dopamine modulation of executive functions: beyond working memory

Cited by 351 publications

References 120 publications

Prenatal cocaine exposure enhances responsivity of locus coeruleus norepinephrine neurons: Role of autoreceptors

Prenatal cocaine exposure enhances responsivity of locus coeruleus norepinephrine neurons: Role of autoreceptors

Ventral Striatal Dopamine Modulation of Different Forms of Behavioral Flexibility

Low Doses of 17α-Estradiol and 17β-Estradiol Facilitate, Whereas Higher Doses of Estrone and 17α- and 17β-Estradiol Impair, Contextual Fear Conditioning in Adult Female Rats

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