The neuroendocrine challenge paradigm provides a “window” on central neurotransmitter function in vivo. This strategy is based on the premise that the sensitivity of certain central receptors can be inferred from the magnitude of the hormonal response to specific pharmacologic probes. For example, the serotonin (5HT) receptor agonist m-chlorophenylpiperazine (m-CPP) stimulates the release of cortisol and prolactin and induces migraine-like headaches. We have previously reported that the headache and cortisol responses to m-CPP are highly correlated, which may implicate a disturbance in central serotonergic neurotransmission in the pathogenesis of migraine. As pharmacologic probes with greater specificity for 5HT receptor subtypes become available, we may be able to elucidate these mechanisms with greater precision. The neuroendocrine challenge methodology is also applicable to the study of other neurotransmitter systems and other headache disorders.
NatteroGCornoMSaviLIsaiaGCPrioloCMussettaMProlactin and migraine: effect of L-dopa on plasma prolactin levels in migraineurs and normals.Headache1986;26;9–12
2.
D'AndreaGCananziARGrigolettoFMeneghiniFCortesiSSoffiatiGThe effect of dopamine receptor agonists on prolactin secretion in childhood migraine.Headache1988;28:354–9
3.
WeizmanAGil-AdIWeizmanRHeringRBecharMTyanoSBasal plasma HGH and cortisol levels and the effect of clonidine administration in female migrainous patients.Neuropsychobiology1984;12:106–11
4.
FacchinettiFMartignoniENappiGFioroniLSancesGGenazzaniARPremenstrual failure of alpha-adrenergic stimulation on hypothalamus-pituitary responses in menstrual migraine.Psychosom Med1989;51;550–8
5.
MartignoniEFacchinettiFRossiFSancesGGenazzaniARNappiGNeuroendocrine evidence of deranged noradrenergic activity in chronic migraine.Psychoneuroendo-crinology1989;14:357–63
6.
GordonMLBrownSLLiptonRBKomMLKaySRSolomonSSerotonergic parallels in migraine, depression, and anxiety. In:NappiGBonoGSandriniGMartignoniEMicieliG, editors.Headache and depression: serotonin pathways as a common clue.New York:Raven Press,1991;21–40
7.
SicuteriFHeadache as possible expression of deficiency of brain 5-hydroxytryptamine (central denervation supersensitivity).Headache1972;12:69–72
8.
FullerRWSerotonin receptors and neuroendocrine responses.Neuropsychopharmacology1990;3:495–502
9.
Van de KarLDCarnesMMaslowskiRJBonadonnaAMRittenhousePAKunimotoKNeuroendocrine evidence for denervation supersensitivity of serotonin receptors: effects of the 5HT agonist RU24969 on corticotropin, corticosterone, prolactin and renin secretion.J Pharmacol Exp Ther1989;251:428–34
10.
van PraagHMLemusCKahnRHormonal probes of central serotonergic activity: do they really exist?Biol Psychiatry1987;22:86–98
11.
YathamLNSteinerMNeuroendocrine probes of serotonergic function: a critical review.Life Sci1993;53:447–63
12.
CacciaSBallabioMSamininRm-Chlorophenylpiperazine, a central 5-hydroxytryptamine agonist, is a metabolite of trazodone.J Pharm Pharmacol1981;33:477–8
13.
SamaninRMenniniTFerrarisABendottiCBorsiniFGarattiniSm-Chlorophenylpiperazine: a central serotonin agonist causing powerful anorexia in rats.Naunyn Schmiedeberg's Arch Pharmacol1979;308:159–63
14.
FullerRWSnoddyHDMasonNROwenJEDisposition and pharmacologic effects of m-chlorophenylpiperazine in rats.Neuropharmacology1981;20:155–62
15.
InvernizziRCotecchiaSDeBlasiAMenniniTPatacciniRSamaninREffects of m-chlorophenylpiperazine on re-ceptor binding and brain metabolism of monoamines in rats.Neurochem Int1981;3:239–44
16.
HamikAPeroutkaSJ1-(m-chlorophenyl)piperazine (mCPP) interactions with neurotransmitter receptors in human brain.Biol Psychiatry1989;25:569–75
17.
KilpatrickGJJonesBJTyersMBIdentification and distribution of 5HT3 receptors in rat brain using radioligand binding.Nature1987;330:746–8
18.
AloiJAInselTRMuellerEAMurphyDLNeuroendocrine and behavioral effects of m-chlorophenylpiperazine administration in rhesus monkeys.Life Sci1984;34:1325–31
19.
MuellerEAMurphyDLSunderlandTNeuroendocrine effects of m-chlorophenylpiperazine, a serotonin agonist, in humans.J Clin Endocrinol Metab1985;61:1179–84
20.
MuellerEAMurphyDLSunderlandTFurther studies of the putative serotonin agonist, m-chlorophenylpiperazine: evidence for a serotonin receptor mediated mechanism of action in humans.Psychopharmacology1986;89:388–91
21.
KahnRSWetzlerSAsnisGMKlingMASuckowRFvan PraagHMEffects of m-chlorophenylpiperazine in normal subjects: a dose response study.Psychopharmacology1990;100:339–44
22.
AulakhCSHillJLMurphyDLEffects of various serotonin receptors subtype-selective antagonists alone and on m-chlorophenylpiperazine-induced neuroendocrine changes in rats.J Pharmacol Exp Ther1992;263:588–95
23.
ZoharJMuellerEAInselTRZohar-KadouchRCMurphyDLSerotonergic responsivity in obsessive-compulsive disorder.Arch Gen Psychiatry1987;44:946–51
24.
HollanderECohenLJDeCariaCSaoudJBSteinDJCooperTBTiming of neuroendocrine responses and effect of m-CPP and fenfluramine plasma levels in OCD.Biol Psychiatry1993;34:407–13
25.
BrewertonTDMurphyDLMuellerEAJimersonDCInduction of migraine-like headaches by the serotonin agonist m-chlorophenylpiperazine.Clin Pharmacol Ther1988;43:605–9
26.
GordonMLLiptonRBBrownSLNakraseiveCRussellMPollackSZHeadache and cortisol responses to m-chlorophenylpiperazine are highly correlated.Cephalalgia1993;13:400–5
PoggioniMBonazziADel BeneESicuteriFFocus on latent nociceptive dysfunction in humans. In:SicuteriFTereniusLVecchietLMaggiCA, editors.Advances in pain research and therapy,Vol. 20.New York:Raven Press,1992:269–80
29.
HodgesJRVellucciSVThe effect of reserpine on hypothalamo-pituitary-adrenocortical function in the rat.Br J Pharmacol1975;53:555–61
30.
SudaTTomoriNYajimaFSumitomoTNakagamiYUshiyamaTTime course study on the effect of reserpine on hypothalamic immunoreactive CRF levels in rats.Brain Res1987;405:247–52
31.
PolleriANappiGMasturzoPMartignoniEMurialdoGBonoGNeuroendocrine approach to headache.Adv Neurol1982;33:173–82
32.
KimballRWFriedmanAPVallejoEEffect of serotonin in migraine patients.Neurology1960;10:107–11
33.
AnthonyMHinterbergerHLanceJWPlasma serotonin in migraine and stress.Arch Neurol1967;16:544–52
34.
CurzonGBarrieMWilkinsonIPRelationships between headache and amine changes after administration of reset-pine to migrainous patients.J Neurol Neurosurg Psychiatry1969;32:555–61
35.
SachsHWolfARussellJAGChristmanDREffect of reserpine on regional cerebral glucose metabolism in control and migraine subjects.Arch Neurol1986;43:1117–23
36.
EcklandDJAEntwisleSJFowlerPAThomasMLettisSYorkMThe effects of sumatriptan, a 5HT1-like agonist, on pituitary adrenal function in healthy volunteers.Br J Clin Pharmacol1992;33:538–9P
37.
MarkianosMLykourasLHatzimanolisJBistolakiEEffects of the serotonin agonist sumatriptan on hormonal plasma levels in healthy and depressed subjects. A placebo controlled study.Neuroendocrinol Lett1994;16:65–71
38.
FowlerPAEntwisleSLettisSYorkMThe effect of sumatriptan on circulating concentrations of prolactin.(Abstract, European Headache Federation 2nd International Conference. Liege, Belgium. June,1994)”
39.
HerdmanJREDelvaNJHockheyRECamplingGMCowenPJNeuroendocrine effects of sumatriptan.Psycho-pharmacology1994;113:561–4
