From Galactorrhea to Osteopenia: Rethinking Serotonin–Prolactin Interactions

Emiliano, Ana B.; Fudge, Julie L.

doi:10.1038/sj.npp.1300412

Cited by 98 publications

(76 citation statements)

References 227 publications

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“…Alternatively, S(ϩ)-MDMA may function as a serotonin releaser but have a more complex pharmacology than a drug that selectively releases serotonin, such as mCPP. In this regard, a complex mechanism involving released dopamine might be predicted to functionally antagonize the effects of released serotonin on prolactin secretion (Emiliano and Fudge, 2004).…”

Section: Effects Of S(ϩ)-mdma (F) Sr(ϯ)-mdma (‚) and R(ϫ)-mdmamentioning

confidence: 99%

Endocrine and Neurochemical Effects of 3,4-Methylenedioxymethamphetamine and Its Stereoisomers in Rhesus Monkeys

Murnane¹,

Fantegrossi²,

Godfrey³

et al. 2010

J Pharmacol Exp Ther

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3,4-Methylenedioxymethamphetamine (MDMA) is an amphetamine derivative that elicits complex biological effects in humans. One plausible mechanism for this phenomenon is that racemic MDMA is composed of two stereoisomers that exhibit qualitatively different pharmacological effects. In support of this, studies have shown that R(Ϫ)-MDMA tends to have hallucinogen-like effects, whereas S(ϩ)-MDMA tends to have psychomotor stimulant-like effects. However, relatively little is known about whether these stereoisomers engender different endocrine and neurochemical effects. In the present study, the endocrine and neurochemical effects of each stereoisomer and the racemate were assessed in four rhesus monkeys after intravenous delivery at doses (1-3 mg/kg) that approximated voluntary self-administration by rhesus monkeys and human recreational users. Specifically, fluorescence-based enzymelinked immunosorbent assay was used to assess plasma prolactin concentrations, and in vivo microdialysis was used to assess extracellular dopamine and serotonin concentrations in the dorsal striatum. R(Ϫ)-MDMA, but not S(ϩ)-MDMA, significantly increased plasma prolactin levels and the effects of S,R(Ϯ)-MDMA were intermediate to each of its component stereoisomers. Although S(ϩ)-MDMA did not alter prolactin levels, it did significantly increase extracellular serotonin concentrations. In addition, S(ϩ)-MDMA, but not R(Ϫ)-MDMA, significantly increased dopamine concentrations. Furthermore, as in the prolactin experiment, the effects of the racemate were intermediate to each of the stereoisomers. These studies demonstrate the stereoisomers of MDMA engender qualitatively different endocrine and neurochemical effects, strengthening the inference that differences in these stereoisomers might be the mechanism producing the complex biological effects of the racemic mixture of MDMA in humans.Racemic 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) is a substituted phenethylamine with significant abuse liability. Although MDMA was placed into Schedule 1 of the Controlled Substances Act, its behavioral effects do not clearly fit into traditional delineations of drugs of abuse. Specifically, the racemic mixture of MDMA has both stimulant and hallucinogen-like effects (Shulgin, 1986;Harris et al., 2002). Moreover, Nichols (1986) postulated that MDMA represented a new class of compounds categorized as "entactogens." In support for this new categorization, Johanson et al. (2006) reported that in a three-choice discrimination procedure approximately half of the human subjects reported that MDMA was similar to the substrate-based dopamine releaser S(ϩ)-amphetamine, whereas the other half reported that it was similar to the serotonin releaser meta-chlorophenylpiperazine (mCPP).Previous studies have suggested that these complex effects are mediated by qualitative differences (i.e., apparent efficacy differences) between MDMA's stereoisomers. For example, one of the earliest studies contrasted the subjective effects of these stereoisomers in humans (A...

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Section: Effects Of S(ϩ)-mdma (F) Sr(ϯ)-mdma (‚) and R(ϫ)-mdmamentioning

confidence: 99%

Endocrine and Neurochemical Effects of 3,4-Methylenedioxymethamphetamine and Its Stereoisomers in Rhesus Monkeys

Murnane¹,

Fantegrossi²,

Godfrey³

et al. 2010

J Pharmacol Exp Ther

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“…An indirect piece of evidence for 5-HT-OT interactions in humans is the well-known prolactin surge associated with fenfluramine challenge (Coccaro et al, 1997;Siever et al, 1984). OT-containing neurons are among the possible mediators of this phenomenon, since OT is a potent prolactin releasing factor (see review by Emiliano and Fudge (2004)). …”

Section: Summary Of Findings and Comparison With Previous Primate Stumentioning

confidence: 99%

“…The sexual dysfunction associated with SSRIs is significant, however (Fava and Rankin, 2002;Rosen et al, 1999), and multiple mechanisms for this have been proposed (see review by Rosen et al, (1999)). It is possible that SSRIstimulated OT expression may also drive prolactin release in some individuals, a phenomenon that is associated with sexual dysfunction (see review by Emiliano and Fudge (2004)). …”

Section: Ot/5-htt Interface Abf Emiliano Et Almentioning

confidence: 99%

The Interface of Oxytocin-Labeled Cells and Serotonin Transporter-Containing Fibers in the Primate Hypothalamus: A Substrate for SSRIs Therapeutic Effects?

Emiliano

Cruz

Pannoni

et al. 2006

Neuropsychopharmacol

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Oxytocin (OT) is a neuropeptide synthesized in the paraventricular (PVN) and supraoptic nuclei (SON) in the hypothalamus. Although OT is more commonly known for its role in the milk-ejection reflex, in recent years research has indicated that OT participates in the expression of social behavior, memory processing, modulation of fear, and stress responses. The demonstration that OT influences affiliative behaviors, such as parental care and reproduction, and decreases anxiety has lead to speculations that it may have a role in mood disorders. Evidence from pharmacologic studies, pointing out the modulation of the OT system by serotonin, has argued in favor of OT as a mediator of serotonin reuptake inhibitors (SSRIs) antidepressant properties. In the present study, we investigated the distribution and overlap of OT-labeled cells and serotonin transporter (5-HTT) immunoreactive (IR) fibers in the Macaque hypothalamus, utilizing immunocytochemical and double-immunofluorescent techniques. Consistent with previous reports, the distribution of OT-labeled cells in the hypothalamus is confined to the PVN and SON. In these nuclei, we demonstrate that the distribution of 5-HTT-labeled fibers follows the distribution of OT-labeled cells. Overlap of OT-labeled neurons and 5-HTT-IR fibers occurs in the parvicellular, magnocellular, dorsal, and posterior subdivisions of the PVN. In the SON, 5-HTT-labeled fibers and OTlabeled cells overlap in the ventromedial subdivision and in the 'capsular' part of the dorsolateral SON. These findings provide neuroanatomic support for the idea that SSRIs' therapeutic effects on social affiliation and anxiety may be mediated in part through components of the OT system. Neuropsychopharmacology (2007) 32, 977-988.

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“…Antidepressants may affect the risk of breast cancer through the influence of prolactin, of which elevated levels have been observed with use of SSRIs, tricyclic antidepressants, and other psychotropic drugs (Amsterdam et al, 1997;Cowen and Sargent, 1997;Emiliano and Fudge, 2004). Higher prolactin levels have been associated with an increased risk of postmenopausal breast cancer (Hankinson et al, 1999;Tworoger et al, 2004).…”

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confidence: 99%

Use of antidepressant medications in relation to the incidence of breast cancer

et al. 2006

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Although associations have been reported between antidepressant use and risk of breast cancer, the findings have been inconsistent. We conducted a population-based case -control study among women enrolled in Group Health Cooperative (GHC), a health maintenance organization in Washington State. Women with a first primary breast cancer diagnosed between 1990 and 2001 were identified (N ¼ 2904) and five controls were selected for each case (N ¼ 14396). Information on antidepressant use was ascertained through the GHC pharmacy database and on breast cancer risk factors and screening mammograms from GHC records. Prior to one year before diagnosis of breast cancer, about 20% of cases and controls had used tricyclic antidepressants (adjusted odds ratio ¼ 1.06, 95% CI 0.94 -1.19) and 6% of each group had used selective serotonin reuptake inhibitors (OR ¼ 0.98, 95% CI 0.80 -1.18). There also were no differences between cases and controls with regard to the number of prescriptions filled or the timing of use. Taken as a whole, the results from this and other studies to date do not indicate an altered risk of breast cancer associated with the use of antidepressants overall, by class, or for individual antidepressants.

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From Galactorrhea to Osteopenia: Rethinking Serotonin–Prolactin Interactions

Cited by 98 publications

References 227 publications

Endocrine and Neurochemical Effects of 3,4-Methylenedioxymethamphetamine and Its Stereoisomers in Rhesus Monkeys

Endocrine and Neurochemical Effects of 3,4-Methylenedioxymethamphetamine and Its Stereoisomers in Rhesus Monkeys

The Interface of Oxytocin-Labeled Cells and Serotonin Transporter-Containing Fibers in the Primate Hypothalamus: A Substrate for SSRIs Therapeutic Effects?

Use of antidepressant medications in relation to the incidence of breast cancer

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