The effects of 5‐HT and m‐chlorophenylpiperazine (m‐CPP) on the efflux of [3H]‐5‐HT from human perfused platelets.

Carver, J G; Grahame‐Smith, D. G.; Johnson, Eddie; Madgwick, Zahra

doi:10.1111/j.1365-2125.1993.tb04172.x

Cited by 15 publications

(3 citation statements)

References 14 publications

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“…20, NO. 3 mCPP Increases Serotonin Release 293 contrast, mCPP does not induce serotonin release from human platelets (Carver et al 1993).…”

Section: Discussionmentioning

confidence: 91%

“…20, NO. 3 mCPP Increases Serotonin Release 293 contrast, mCPP does not induce serotonin release from human platelets (Carver et al 1993).When interpreting the data obtained in clinical studies using mCPP as a pharmacological tool, the possibility that the effects of the drug, at least partly, are caused by the release of endogenous serotonin should be considered. Thus, whereas previous discussions on the mode of action of mCPP have focused on the serotonin receptor subtypes for which the compound displays affinity, the finding that mCPP is an indirect serotonin agonist implies that all serotonin receptors situated in the vicinity of serotonergic nerve terminals, and not concomitantly antagonized by mCPP, may be activated by the drug.…”

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confidence: 99%

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Effects of mCPP on the Extracellular Concentrations of Serotonin and Dopamine in Rat Brain

Eriksson

Engberg²,

Bing³

et al. 1999

Neuropsychopharmacology

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Intravenous administration of m-chloro-phenylpiperazine (mCPP) (0.25 or 2.5 mg/kg) induced a marked and doserelated increase in extracellular concentrations of serotonin in hippocampus (300-1,400% of baseline) as measured using in vivo microdialysis in awake male Wistar rats of the spontaneously hypertensive (SH) strain. Indicating that the effect of mCPP was caused by a reversal of the serotonin transporter, it was antagonized by pretreatment with the serotonin re-uptake inhibitor citalopram (10 mg/kg) but was unaffected by local administration of the sodium channel blocker tetrodotoxin (TTX; 1 m). mCPP was also shown to induce an increase in extracellular concentrations of dopamine in the nucleus accumbens and the striatum of SH rats and in the nucleus accumbens of rats of the Sprague-Dawley (SD) Dopamine, In vivo microdialysis; Hippocampus; Striatum, Nucleus accumbens; Citalopram; Rat m-Chloro-phenylpiperazine (mCPP), the metabolite of the antidepressant drug trazodone, has recently gained marked attention as a putative probe of serotonergic function in clinical psychiatric research. Thus, the prolactin, ACTH, and cortisol responses to mCPP frequently have been used as putative markers of postsynaptic serotonin receptor function in various psychiatric disorders. Moreover, administration of mCPP has been shown to elicit, and/or aggravate, anxiety attacks in patients with panic disorder, obsessions in patients with obsessive compulsive disorder (OCD), elation in alcoholics and cocaine addicts, and positive symptoms in schizophrenic patients (see Murphy et al. 1991;Kahn and Wetzler 1991;Krystal et al. 1993;Buydens-Branchey et al. 1993;Krystal et al. 1994).mCPP displays high affinity to 5-HT2C receptors and moderate, or low, affinity to 5-HT1A, 5-HT1B, 5-HT2A, 5-HT2B, and 5-HT3 receptors; in addition, the compound has some affinity for alpha-2-adrenoceptors. At the 5-HT2C receptor, mCPP seems to act as a partial agonist with relatively high intrinsic efficacy, whereas, at the other serotonin receptors, the intrinsic efficacy of mCPP is moderate or low (see Murphy et al. 1991 NO . 3 and Wetzler 1991). The behavioral and endocrine effects of mCPP observed in clinical studies are generally attributed to the direct effects of mCPP on various subtypes of serotonin receptors; in contrast, little attention has been paid to the report by Baumann et al. (1993) suggesting that mCPP may also stimulate serotonin release by means of an interaction with the serotonin transporter (see also Baumann et al. 1995).To further elucidate the possible influence of mCPP on the release of serotonin, we studied the effects of a high dose of mCPP on extracellular, hippocampal concentrations of serotonin in awake, freely moving rats using in vivo microdialysis.Enhanced dopaminergic neurotransmission has been suggested as a mechanism of importance both for the positive symptoms of schizophrenia and for the euphoria induced by such central stimulants as cocaine. The observations that mCPP may aggravate psychotic symptoms in schizophr...

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“…20, NO. 3 mCPP Increases Serotonin Release 293 contrast, mCPP does not induce serotonin release from human platelets (Carver et al 1993).…”

Section: Discussionmentioning

confidence: 91%

mentioning

confidence: 99%

Effects of mCPP on the Extracellular Concentrations of Serotonin and Dopamine in Rat Brain

Eriksson

Engberg²,

Bing³

et al. 1999

Neuropsychopharmacology

View full text Add to dashboard Cite

show abstract

“…MCPP interacts with numerous 5HT receptor, subtype and the 5HT transporter. It acts as an antagonist at the 5HT‐3 receptor, 86,87 as a partial agonist at the 5HT‐1 receptor, 89–90 and as a partial agonist or antagonist at the 5HT‐2 receptor 91–93 . MCPP has relatively low affinity for alpha 1 , alpha 2 , dopamine 1, and dopamine 2 receptors 94,95 .…”

Section: Clinical Neurobiologic Researchmentioning

confidence: 99%

Noradrenergic Alterations in Posttraumatic Stress Disorder

Southwick

Morgan

Bremner

et al. 1997

Annals of the New York Academy of Sciences

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Since World War I, numerous clinicians and researchers have described signs and symptoms of sympathetic nervous system dysregulation in combat veterans who suffer from what is currently termed posttraumatic stress disorder (PTSD). These veterans return from war in a hyperaroused, vigilant, and at times agitated state that may persist or even worsen over time. To describe this chronic war-related physiologic hyperarousal, Kardiner and Spiegel' coined the term physioneurosis in the 1940s. They believed that physioneurosis differed from other neuroses in its profound underlying physiologic basis. Similarly, Grinker and Spiege12 believed that veterans with physioneurosis suffered from chronic stimulation of the sympathetic nervous system that made them appear as if they had received an injection of adrenaline.Formal research into the nature of war-related neurobiologic alterations in sympathetic nervous system activity began as early as 1918 when Meakins and Wilson3 exposed shell-shocked veterans to the sounds of gunfire and the smell of sulfuric fumes. Compared to healthy controls, shell-shocked veterans showed significantly greater increases in heart rate. Also in 1918, among combat veterans with shell shock, Fraser and Wilson4 reported exaggerated increases in subjective anxiety, heart rate, and blood pressure after administration of epinephrine (EPI). Since then, a host of well-designed psychophysiologic studies have demonstrated increased physiologic reactivity to reminders of past traumas in individuals with PTSD compared to cont r o l~.~'~

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Specificity of Ethanollike Effects Elicited by Serotonergic and Noradrenergic Mechanisms

Krystal

Webb²,

Cooney³

et al. 1994

Arch Gen Psychiatry

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m-Chlorophenylpiperazine produced ethanollike effects and alcohol craving in recently detoxified alcoholics. Yohimbine increased Sensation Scale scores but was not recognized as ethanollike by patients. Although both drugs produced comparable levels of nervousness, yohimbine did not increase craving for alcohol. These data further implicate serotonergic systems in the discriminative properties of ethanol and may indicate a serotonergic contribution to craving. Noradrenergic systems contributed to the discriminative properties of ethanol but not to those features of ethanol response that were salient to craving in this population.

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The effects of 5‐HT and m‐chlorophenylpiperazine (m‐CPP) on the efflux of [3H]‐5‐HT from human perfused platelets.

Abstract: 1 m-Chlorophenylpiperazine (m-CPP), a S-HTic-receptor agonist, induces migrainelike headaches when taken orally by migraine sufferers.

Cited by 15 publications

References 14 publications

Effects of mCPP on the Extracellular Concentrations of Serotonin and Dopamine in Rat Brain

Effects of mCPP on the Extracellular Concentrations of Serotonin and Dopamine in Rat Brain

Noradrenergic Alterations in Posttraumatic Stress Disorder

Specificity of Ethanollike Effects Elicited by Serotonergic and Noradrenergic Mechanisms

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