D<sub>1</sub> dopamine receptor stimulation increases GluR1 phosphorylation in postnatal nucleus accumbens cultures

Chao, Steven; Lu, Wenxiao; Lee, Hey Kyoung; Huganir, Richard L.; Wolf, Marina E.

doi:10.1046/j.1471-4159.2002.00877.x

Cited by 93 publications

(92 citation statements)

References 58 publications

(68 reference statements)

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“…Indeed it is interesting to note that administrations of the D1 receptor antagonist induced similar behavioral patterns (ie a selective impairment in the reactivity to the spatial change) when injected into the PFC or the nucleus accumbens. There is now consistent experimental evidence suggesting that striatal glutamate receptor-channels undergo states of phosphorylation and dephosphorylation that can prolong or shorten the time of activation of the channels (Colwell and Levine, 1995;Umemiya and Raymond, 1997) and that these changes are under the control of D1 DA receptors (Chao et al, 2002). Such processes could explain the facilitatory effects of D1 receptors on the short-term processing of spatial information in the two structures.…”

Section: Prefrontal Cortex Dopamine In Spatial Learningmentioning

confidence: 87%

D1 and D2 Receptor Antagonist Injections in the Prefrontal Cortex Selectively Impair Spatial Learning in Mice

Rinaldi

Mandillo

Oliverio

et al. 2006

Neuropsychopharmacol

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The prefrontal cortex (PFC) is a cortical area involved in selecting and retaining information to produce complex behaviors. Within the PFC, the dopaminergic system plays an important role in information processing. Thus, the objective of this study was to test whether bilateral administration of the D1 and D2 receptor antagonists in the prelimbic region of the PFC influenced the performance of mice in a non-associative spatial learning task. CD1 mice were bilaterally microinjected in the PFC with either the D1 receptor antagonist, SCH23390 (SCH 6.25; 12.5; 50 ng), or the D2 receptor antagonist, sulpiride (SULP 12.5; 50; 100 ng) and placed into an open field containing five different objects. After three sessions of habituation two objects were repositioned (spatial change) and in the subsequent session one of the objects was substituted (non-spatial change). No significant alteration was observed in the habituation pattern of the animals after D1 or D2 receptor blockade. When two of the objects were displaced, control mice explored the displaced objects far more than the non-displaced ones, while mice treated with SCH or SULP spent a comparable amount of time re-exploring the two object categories. Conversely, DA antagonists had no effects on the discrimination of the new object. Thus, the administration of both SCH and SULP selectively impaired the ability of mice to discriminate a spatial change, without affecting any other behavioral parameter. These findings could provide a model to study the role of the PFC dopaminergic system in spatial learning and to study the neural mechanisms underlying cognitive and attention deficits often observed in psychiatric disorders.

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Section: Prefrontal Cortex Dopamine In Spatial Learningmentioning

confidence: 87%

D1 and D2 Receptor Antagonist Injections in the Prefrontal Cortex Selectively Impair Spatial Learning in Mice

Rinaldi

Mandillo

Oliverio

et al. 2006

Neuropsychopharmacol

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“…This suggests that low doses of naloxone might be insufficient to activate signaling pathways required for phosphorylation of CREB and GluR1. Both PKA and glutamate-mediated increases in Ca 2ϩ are necessary for CREB activation, but only PKA can induce GluR1 phosphorylation at Ser 845 (Sheng et al, 1991;Chao et al, 2002a). Thus, naloxone-induced P-CREB in morphine-dependent rats might reflect synergism between signaling from withdrawal-induced glutamate release (Sepulveda et al, 1998) and increased cAMP.…”

Section: Dissociation Of Motivational and Somatic Withdrawal Signsmentioning

confidence: 99%

Behavioral and Molecular Effects of Dopamine D1 Receptor Stimulation during Naloxone-Precipitated Morphine Withdrawal

Chartoff

Mague

Barhight

et al. 2006

Journal of Neuroscience

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Morphine dependence is characterized by somatic and motivational signs of withdrawal that likely contribute to the maintenance of addictive behavior. The nucleus accumbens (NAc) receives extensive dopaminergic input and is an important substrate for mediating these aversive states. In the NAc, the function of the transcription factor cAMP response element binding protein (CREB) and AMPA glutamate receptor subunit, type 1 (GluR1) can be regulated by dopamine (DA) D 1 receptor-mediated phosphorylation (P-CREB, P-GluR1). However, the roles of D 1 receptors, CREB, and GluR1 in morphine dependence are not well understood. Here, we show that somatic signs of naloxone-precipitated withdrawal were associated with increased P-CREB, but not P-GluR1, in the NAc of morphinedependent rats. The D 1 receptor agonist chloro-APB hydrobromide (SKF 82958) was rewarding in morphine-dependent rats and blocked naloxone-induced place aversions and somatic signs of withdrawal. Surprisingly, SKF 82958 increased P-GluR1, but not P-CREB, in the NAc, and naloxone reduced SKF 82958-mediated P-GluR1 induction specifically in morphine-dependent rats. Together, these results confirm that aversive treatments can increase CREB function in the NAc. Furthermore, they suggest a dependence-associated shift in the molecular mechanisms that regulate the consequences of D 1 receptor stimulation, favoring activation of GluR1 rather than CREB. These data raise the possibility that the rewarding effects of SKF 82958 in morphine-dependent rats involve increased P-GluR1 in the NAc, although the involvement of other brain regions cannot be ruled out. Regardless, these findings suggest for the first time that D 1 agonists might be useful for the treatment of withdrawal symptoms that contribute to the maintenance of opiate addiction in humans.Key words: nucleus accumbens; CREB; GluR1; AMPA; place conditioning; SKF 82958 IntroductionOpiate withdrawal causes somatic abstinence signs as well as a motivational syndrome characterized by dysphoria and depression (Koob and Le Moal, 1997;De Vries and Shippenberg, 2002) in humans. These negative affective states are thought to contribute to addictive behaviors (Koob and Le Moal, 1997;Markou et al., 1998). The nucleus accumbens (NAc), which receives extensive dopaminergic input, plays a key role in opiate reward (Wise, 1989) as well as the motivational and somatic signs of opiate withdrawal (Koob et al., 1992;Harris and Aston-Jones, 1994). The opioid receptor antagonist naloxone precipitates physical withdrawal signs in morphine-dependent rats and produces behaviors, such as conditioned place aversions, that reflect aversive states mediated within the NAc (Stinus et al., 1990).Acute morphine decreases formation of cAMP (Childers, 1991), whereas chronic morphine causes super-sensitivity of cAMP pathways in areas including the NAc (Nestler and Aghajanian, 1997). Precipitated opiate withdrawal unmasks upregulated cAMP pathways, which likely contribute to aversive states. Hypothetically, activation of dopamine (DA) D 1 rece...

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“…D1/D5 receptor activation leads to increased cyclic AMP levels and increased PKA activity (17), favoring phosphorylation of GluR1 (54) and AMPA receptor insertion into extrasynaptic sites (19). This may explain why D1/D5-selective agonists prevent LTD (55) and facilitate the induction of LTP (41).…”

Section: D1/d5 Receptors Protect Synapses From A␤ Oligomersmentioning

confidence: 99%

Activation of D1/D5 Dopamine Receptors Protects Neurons from Synapse Dysfunction Induced by Amyloid-β Oligomers

Jürgensen

Antônio

Mussi

et al. 2011

Journal of Biological Chemistry

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Soluble oligomers of the amyloid-␤ peptide (A␤Os) accumulate in the brains of Alzheimer disease (AD) patients and are implicated in synapse failure and early memory loss in AD. A␤Os have been shown to impact synapse function by inhibiting long term potentiation, facilitating the induction of long term depression and inducing internalization of both AMPA and NMDA glutamate receptors, critical players in plasticity mechanisms. Because activation of dopamine D1/D5 receptors plays important roles in memory circuits by increasing the insertion of AMPA and NMDA receptors at synapses, we hypothesized that selective activation of D1/D5 receptors could protect synapses from the deleterious action of A␤Os. We show that SKF81297, a selective D1/D5 receptor agonist, prevented the reduction in surface levels of AMPA and NMDA receptors induced by A␤Os in hippocampal neurons in culture. Protection by SKF81297 was abrogated by the specific D1/D5 antagonist, SCH23390. Levels of AMPA receptor subunit GluR1 phosphorylated at Ser 845 , which regulates AMPA receptor association with the plasma membrane, were reduced in a calcineurin-dependent manner in the presence of A␤Os, and treatment with SKF81297 prevented this reduction. Establishing the functional relevance of these findings, SKF81297 blocked the impairment of long term potentiation induced by A␤Os in hippocampal slices. Results suggest that D1/D5 receptors may be relevant targets for development of novel pharmacological approaches to prevent synapse failure in AD. Alzheimer disease (AD)2 is the main cause of dementia among the elderly, and current estimates indicate that it affects around 25 million people worldwide (1, 2). Although much is known about the pathophysiology of AD, there is still no cure or effective treatment capable of slowing the progression of the disease. For this reason, development of novel pharmacological strategies for treatment is of critical importance.Considerable evidence indicates that soluble oligomers of the amyloid-␤ peptide (A␤Os) accumulate in the brains of AD patients and are responsible for synapse dysfunction and memory loss in AD (3-5). Among other deleterious actions, A␤Os impair synaptic plasticity, likely leading to memory loss at early stages of the disease. A␤Os have been shown to inhibit long term potentiation (LTP) (4, 6, 7), facilitate the induction of long term depression (LTD) (8, 9), induce internalization of , and increase activation of protein phosphatases, such as calcineurin and protein phosphatase-1 (9, 10, 15, 16), finally leading to spine loss (14).Dopamine receptors have been grouped into two families: D1-type and D2-type (17). The D1 family comprises D1 and D5 receptor subtypes, which are mostly coupled to G␣ s and stimulate production of the second messenger cyclic AMP, leading to activation of protein kinase A (PKA) (17). D1/D5 receptors play important roles in cognition, mediating plasticity and specific aspects of cognitive function, including working and spatial learning and memory processes (18). Stimulation of D...

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D₁ dopamine receptor stimulation increases GluR1 phosphorylation in postnatal nucleus accumbens cultures

Cited by 93 publications

References 58 publications

D1 and D2 Receptor Antagonist Injections in the Prefrontal Cortex Selectively Impair Spatial Learning in Mice

D1 and D2 Receptor Antagonist Injections in the Prefrontal Cortex Selectively Impair Spatial Learning in Mice

Behavioral and Molecular Effects of Dopamine D1 Receptor Stimulation during Naloxone-Precipitated Morphine Withdrawal

Activation of D1/D5 Dopamine Receptors Protects Neurons from Synapse Dysfunction Induced by Amyloid-β Oligomers

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D1 dopamine receptor stimulation increases GluR1 phosphorylation in postnatal nucleus accumbens cultures

Cited by 93 publications

References 58 publications

D1 and D2 Receptor Antagonist Injections in the Prefrontal Cortex Selectively Impair Spatial Learning in Mice

D1 and D2 Receptor Antagonist Injections in the Prefrontal Cortex Selectively Impair Spatial Learning in Mice

Behavioral and Molecular Effects of Dopamine D1 Receptor Stimulation during Naloxone-Precipitated Morphine Withdrawal

Activation of D1/D5 Dopamine Receptors Protects Neurons from Synapse Dysfunction Induced by Amyloid-β Oligomers

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D₁ dopamine receptor stimulation increases GluR1 phosphorylation in postnatal nucleus accumbens cultures