Sumatriptan Inhibits Synaptic Transmission in the Rat Midbrain Periaqueductal Grey

Abstract

Background: There is evidence to suggest that the midbrain periaqueductal grey (PAG) has a role in migraine and the actions of the anti-migraine drug sumatriptan. In the present study we examined the serotonergic modulation of GABAergic and glutamatergic synaptic transmission in rat midbrain PAG slices in vitro.

Serotonergic modulation of neuronal activity in rat midbrain periaqueductal gray

“…This was likely to be mediated by a presynaptic mechanism because the increase in evoked IPSCs was associated with a change in their pairedpulse ratio. This differs from and would functionally oppose the 5-HT 1A -and 5-HT 1B/D -induced presynaptic inhibition that we and others have observed previously within the PAG and DRN (Jeong et al 2008;Kishimoto et al 2001;Lemos et al 2006). It can be noted that this 5-HT 2A/C -mediated presynaptic enhancement was observed in the lateral and dorsolateral PAG, the columns in which the 5-HT 2A/C -induced postsynaptic depolarization was most prominent.…”

“…We have previously demonstrated that 5-HT inhibits GABAergic synaptic transmission within PAG and that this is mimicked by 5-HT 1A receptor agonists as well as sumatriptan and 5-HT 1B/D receptor agonists (Jeong et al 2008). Given the above finding that 5-HT 2A/C agonists have postsynaptic effects on PAG neurons, we also examined whether DOI modulates GABAergic synaptic transmission.…”

“…Stock solutions of all drugs were prepared in distilled water, or dimethyl sulfoxide, and then diluted (1:3,000 to 1:10,000, final vehicle concentration 0.01-0.033% vol/vol) to working concentrations using ACSF and applied by superfusion. Supramaximal concentrations of agonists and antagonists were used (as in Jeong et al 2008). 1,4-Dihydro-3-(1,2,3,6-tetrahydro-4-pyridinyl)-5H-pyrrol [3,2-b]pyridin-5-one dihydrochloride (CP 93129), 2-[5- [3-(4-methylsulfonylamino)…”

“…The PAG contains varying levels of 5-HT 1A/B/D/F and 5-HT 2A/C receptor mRNA and protein (Bonaventure et al 1998;Bruinvels et al 1993Bruinvels et al , 1994Castro et al 1997;Jeong et al 2008;Pompeiano et al 1992Pompeiano et al , 1994. Cellular in vitro studies have shown that activation of 5-HT 1A , -B , and -D receptors presynaptically inhibits synaptic transmission within the PAG (Jeong et al 2008;Kishimoto et al 2001).…”

“…Cellular in vitro studies have shown that activation of 5-HT 1A , -B , and -D receptors presynaptically inhibits synaptic transmission within the PAG (Jeong et al 2008;Kishimoto et al 2001). Whereas it has been shown that postsynaptic 5-HT 1A receptor activation opens an inwardly rectifying potassium conductance in acutely isolated PAG neurons (Jeong et al 2001), postsynaptic 5-HT 1A actions have not been examined in intact PAG slices, and the role of other 5-HT 1 receptor subtypes and of 5-HT 2 receptors has not been examined.…”