Reboxetine modulates norepinephrine efflux in the frontal cortex of the freely moving rat: the involvement of α2 and 5-HT1A receptors

Owen, Jenny C.E.; Whitton, Peter S.

doi:10.1016/s0304-3940(03)00792-4

Cited by 7 publications

(6 citation statements)

References 10 publications

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“…Like yohimbine, selective NE reuptake inhibitors such as atomoxetine can increase synaptic NE (Owen and Whitton 2003). However, their effects on integrated NE function relative to impulsive behavior are quite different from those of yohimbine.…”

Section: Discussionmentioning

confidence: 99%

“…Yohimbine, an alpha-2 antagonist, has opposite effects. Further, it blocks the feedback regulation by alpha-2 receptors of NE release, which limits the increase in overall NE function associated with NE reuptake blockade, resulting in reversal of the reduction in NE release by atomoxetine (Owen and Whitton 2003). Therefore, compared to atomoxetine, yohimbine increases net NE release, and blocks any direct behavioral effect of alpha-2 receptor stimulation.…”

Section: Discussionmentioning

confidence: 99%

“…For example, blockade of NE reuptake increases synaptic NE, but firing rate and NE release are reduced by stimulation of presynaptic alpha-2 autoreceptors; this reduction in NE release is prevented by alpha-2 antagonists (Owen and Whitton 2003). …”

Section: Introductionmentioning

confidence: 99%

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Norepinephrine and impulsivity: effects of acute yohimbine

et al. 2013

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Rationale Rapid-response impulsivity, characterized by inability to withhold response to a stimulus until it is adequately appraised, is associated with risky behavior and may be increased in a state-dependent manner by norepinephrine. Objective We assessed effects of yohimbine, which increases norepinephrine release by blocking alpha-2 noradrenergic receptors, on plasma catecholamine metabolites, blood pressure, subjective symptoms, and laboratory-measured rapid-response impulsivity. Methods Subjects were twenty-three healthy controls recruited from the community, with normal physical examination and ECG, and negative history for hypertension, cardiovascular illness, and Axis I or II disorder. Blood pressure, pulse, and behavioral measures were obtained before and periodically after 0.4 mg/kg oral yohimbine or placebo in a randomized, counterbalanced design. Metabolites of norepinephrine (3-methoxy-4-hydroxyphenylglycol, MHPG; vanillylmandelic acid, VMA) and dopamine (homovanillic acid, HVA) were measured by high pressure liquid chromatography with electrochemical detection. Rapid-response impulsivity was measured by commission errors and reaction times on the Immediate Memory Task (IMT), a continuous performance test designed to measure impulsivity and attention. Results Yohimbine increased plasma MHPG and VMA but not HVA. Yohimbine increased systolic and diastolic blood pressure and pulse rate. On the IMT, yohimbine increased impulsive errors and impulsive response bias and accelerated reaction times. Yohimbine-associated increase in plasma MHPG correlated with increased impulsive response rates. Time courses varied; effects on blood pressure generally preceded those on metabolites and test performance. Conclusions These effects are consistent with increased rapid-response impulsivity after pharmacological noradrenergic stimulation in healthy controls. Labile noradrenergic responses, or increased sensitivity to norepinephrine, may increase risk for impulsive behavior.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Norepinephrine and impulsivity: effects of acute yohimbine

et al. 2013

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“…This hypothesis is consistent with our previous studies which demonstrated that combined administration of the 5-HT 1A agonist R(+)-8-OH-DPAT with either a selective 5-HT 2A antagonist, MDL 100907, or D 2 antagonist S(-)-sulpiride, could augment DA efflux in rat PFC Data from Owens et al 2001;Gobert et al 1999;and Millan et al 2001 SERT Serotonin transporter, NET norepinephrine transporter, DAT dopamine transporter, 5-HT serotonin receptor, α 1 adrenergic α 1 receptor, M 1 muscarinic 1 receptor, H 1 histamine 1 receptor (Ichikawa and Meltzer 1999;Ichikawa et al 2001b). A similar mechanism may contribute to enhanced NE efflux since systemic administration of 5-HT 1A receptor agonists increase NE efflux in the rat PFC through activation of postsynaptic 5-HT 1A heteroreceptors (Hajos-Korcsok et al 1999;Ago et al 2002;Owen and Whitton 2003). The results of the present study also showed that the 5-HT 1A antagonist WAY 100635 could partly inhibit the augmentation of combined administration of risperidone and citalopram on both DA and NE efflux in mPFC, providing additional evidence to support this hypothesis.…”

Section: Discussionmentioning

confidence: 99%

Augmentation by citalopram of risperidone-induced monoamine release in rat prefrontal cortex

Huang

Ichiwaka

et al. 2006

Psychopharmacology

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“…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 . As previously noted, ASE is a potent 5-HT 2C -receptor and a 2 -adrenoceptor antagonist (Schotte et al, 1996;Shahid et al, 2007).…”

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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Reboxetine modulates norepinephrine efflux in the frontal cortex of the freely moving rat: the involvement of α2 and 5-HT1A receptors

Cited by 7 publications

References 10 publications

Norepinephrine and impulsivity: effects of acute yohimbine

Norepinephrine and impulsivity: effects of acute yohimbine

Augmentation by citalopram of risperidone-induced monoamine release in rat prefrontal cortex

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

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