Amphetamine-induced locomotion, behavioral sensitization to amphetamine, and striatal D2 receptor function in rats with high or low spontaneous exploratory activity: Differences in the role of locus coeruleus

Alttoa, Aet; Eller, Marika; Herm, Laura; Rinken, Ago; Harro, Jaanus

doi:10.1016/j.brainres.2006.10.075

Cited by 44 publications

(22 citation statements)

References 49 publications

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“…We have shown that these two groups display, respectively, high and low levels of anxiety in several other behavioural tests and respond differently to certain pharmacological manipulations. For example, treatment with the neurotoxin DSP-4 which is selective to the locus coeruleus noradrenergic projections had different effects on spontaneous, amphetamine-stimulated (Alttoa et al, 2005) and amphetamine-sensitized (Alttoa et al, 2007) behaviour in LE- and HE-rats. DSP-4 treatment also decreased the ex vivo 5-hydroxyindoleacedic acid levels in the nucleus accumbens and striatum in LE-rats only.…”

Section: Introductionmentioning

confidence: 99%

Regulation of extracellular serotonin levels and brain-derived neurotrophic factor in rats with high and low exploratory activity

et al. 2008

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Serotonin (5-HT) system has a significant role in anxiety- and depression-related states and may be influenced by brain-derived neurotrophic factor (BDNF). This study examined extracellular 5-HT levels and expression of BDNF in rats with persistently low or high levels of exploratory activity (LE and HE, respectively). Baseline extracellular levels of 5-HT as assessed by in vivo microdialysis in conscious animals were similar in both groups in medial prefrontal cortex (PFC) and dentate gyrus (DG). No differences were found in parachloroamphetamine-induced 5-HT release in either region. However, LE animals had significantly higher levels of 5-HT transporter (5-HTT) binding in PFC and a larger increase in extracellular 5-HT levels after administration of citalopram (1 μM) into this area by retrograde dialysis. No difference in 5-HTT levels was found in hippocampus, while perfusion with citalopram was accompanied by a greater increase in extracellular 5-HT in the HE group in this brain region. LE-rats had higher levels of BDNF mRNA in the PFC but not hippocampus. In contrast, levels of nerve growth factor mRNA were similar in these brain regions of LE- and HE-rats. The differential regulation of 5-HT-ergic system in LE- and HE-rats in PFC and hippocampus may form the basis for their distinct anxiety-related behaviours.

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Section: Introductionmentioning

confidence: 99%

Regulation of extracellular serotonin levels and brain-derived neurotrophic factor in rats with high and low exploratory activity

et al. 2008

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“…However the exact role of the receptors in these processes require additional clarification and therefore different animal models are used [6][7][8]. There are available several methods for the characterization of receptor expression and transmitter accumulation levels in animals, but information about the state of signal transduction system of receptors of interest has remained scarce.…”

Section: Resultsmentioning

confidence: 99%

“…Thus, it has been shown that one important factor for the development of D 2 supersensitivity after 6-OHDA induced lesions of the striatal DA system is connected with increased activity of G proteins, which in turn is caused by decreased affinity of GDP [6]. Correlations between animal behavior and D 2 -specific signal transduction has also been found in the case of amphetamine-induced locomotion [7] and sucrose intake of O. Pulges Á A. Rinken (&) Institute of Organic and Bioorganic Chemistry, University of Tartu, Jakobi Str.…”

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confidence: 91%

α2A-Adrenoceptor-specific Stimulation of [35S]GTPγS Binding to Membrane Preparations of Rat Frontal Cortex

Pulges

Rinken

2007

Neurochem Res

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Functional activation of alpha 2A adrenergic receptors in the crude membranes from rat frontal cortex was studied by a [35S]-guanosine 5'-O-(gamma-thiotriphosphate) ([35S]GTP gamma S) binding assay. alpha 2A agonists UK14304 and guanfacine decreased the ability of GDP to compete with [35S]GTP gamma S binding to the membranes and 0.1 mM GDP was found to be optimal for the following functional experiments. However, even after careful optimization of experimental conditions the specificity of ligands for rat alpha 2 adrenoceptors were not sufficient, as agonists as well as antagonists became activators of other signal transduction systems before achieving their maximal effect in the alpha 2A-adrenergic system. Only using compromising concentration of agonist (up to 1 microM UK14304) and antagonist (up to 1 microM RS79948) to inhibit agonist's effect, allowed us to filtrate out alpha 2A specific effect for characterization of signal transduction in rat frontal cortex membranes for the comparison efficacies of this system for different animals from behavioral experiments.

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“…In contrast, several studies have described psychostimulant-induced changes that take place downstream from G-protein-coupled dopamine receptors (GPCRs). These changes include altered G-protein coupling (Alttoa et al, 2007, Bailey et al, 2008), hyperactivity of adenylyl cyclase (Borgkvist and Fisone, 2007), changes in phosphorylation cascades (Borgkvist and Fisone, 2007, Zhai et al, 2008), and altered function of GPCR-associated ion channels (Kobayashi et al, 2004). Therefore, studying changes in D1 and D2 receptor-driven G-protein signaling is central to understanding psychostimulant-induced neural adaptations.…”

Section: Introductionmentioning

confidence: 99%

Amphetamine up-regulates activator of G-protein signaling 1 mRNA and protein levels in rat frontal cortex: the role of dopamine and glucocorticoid receptors

Schwendt

McGinty

2010

Neuroscience

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Acute and chronic exposure to psychostimulants results in altered function of G-protein-coupled receptors in the forebrain. It is believed that neuroadaptations in G-protein signaling contribute to behavioral sensitivity to psychostimulants that persists over a prolonged drug-free period. Proteins termed activators of G-protein signaling (AGS) have been characterized as potent modulators of both receptor-dependent and receptor-independent G-protein signaling. Nevertheless, the regulation of AGS gene and protein expression by psychostimulants remains poorly understood. In the present study, we investigated amphetamine (AMPH)-induced changes in expression patterns of several forebrain-enriched AGS proteins. A single exposure to AMPH (2.5 mg/kg i.p.) selectively induced gene expression of AGS1, but not Rhes or AGS3 proteins, in the rat prefrontal cortex (PFC) as measured 3h later. Induction of AGS1 mRNA in the PFC by acute AMPH was transient and dose-dependent. Even repeated treatment with AMPH for 5 days did not produce lasting changes in AGS1 mRNA and protein levels in the PFC as measured three weeks post treatment. However, at this time point, a low dose AMPH challenge (1 mg/kg, i.p.) induced a robust behavioral response and up-regulated AGS1 expression in the PFC selectively in animals with an AMPH history. The effects of AMPH on AGS1 expression in the PFC were blocked by a D2, but not D1, dopamine receptor antagonist and partially by a glucocorticoid receptor antagonist. Collectively, the present study suggests that (1) AGS1 represents a regulator of G-protein signaling that is rapidly inducible by AMPH in the frontal cortex, (2) AGS1 regulation in the PFC parallels behavioral activation by acute AMPH in drug-naïve animals and hypersensitivity to AMPH challenge in sensitized animals, and (3) D2 dopamine and glucocorticoid receptors regulate AMPH effects on AGS1 in the PFC. Changes in AGS1 levels in the PFC may result in abnormal receptor-to-G-protein coupling that alters cortical sensitivity to psychostimulants.

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Amphetamine-induced locomotion, behavioral sensitization to amphetamine, and striatal D2 receptor function in rats with high or low spontaneous exploratory activity: Differences in the role of locus coeruleus

Cited by 44 publications

References 49 publications

Regulation of extracellular serotonin levels and brain-derived neurotrophic factor in rats with high and low exploratory activity

Regulation of extracellular serotonin levels and brain-derived neurotrophic factor in rats with high and low exploratory activity

α2A-Adrenoceptor-specific Stimulation of [35S]GTPγS Binding to Membrane Preparations of Rat Frontal Cortex

Amphetamine up-regulates activator of G-protein signaling 1 mRNA and protein levels in rat frontal cortex: the role of dopamine and glucocorticoid receptors

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