Effect of ergotamine on serotonin-mediated responses in the rodent and human brain.
In the rat dorsal hippocampus and dorsal raphe nucleus, the microiontophoretic application of ergotamine and 5-HT suppressed the firing activity of CA3 pyramidal neurons and 5-HT neurons, an effect antagonized by selective 5-HT1A receptor antagonists. Co-application of ergotamine prevented the inhibitory action of 5-HT on the firing activity of CA3 pyramidal neurons but not of 5-HT neurons, indicating that ergotamine acted as a partial 5-HT1A receptor agonist in the dorsal hippocampus and as a full agonist at 5-HT1A autoreceptors. Ergotamine decreased, in a concentration-dependent manner, the electrically evoked release of [3H]5-HT in preloaded rat and guinea pig hypothalamus slices; this effect was prevented by the nonselective 5-HT receptor antagonist methiothepin but not by the selective 5-HT1B/1D receptor antagonist GR 127935 or the alpha 2-adrenoceptor antagonist idazoxan. Although body temperature in humans remained unchanged following inhaled ergotamine, in the rat, subcutaneously injected ergotamine produced a hypothermia that was prevented by a pretreatment with the 5-HT1A/1B receptor/beta-adrenoceptor antagonist pindolol. Finally in humans, ergotamine did not alter prolactin or adrenocorticotropic hormone levels, but increased growth hormone level, which was prevented by pindolol. Cortisol level was increased in humans by ergotamine, but this enhancement was unaltered by pindolol. In conclusion, the present results suggest that ergotamine acted in the rat brain as a 5-HT1A receptor agonist and as an agonist of terminal 5-HT autoreceptor of a yet undefined subtype. In humans, ergotamine also displayed some 5-HT1A receptor activity but, probably because of lack of receptor selectivity, it did not present the same profile as other 5-HT1A receptor agonists.
McGill University, Department of Psychiatry, Montréal, Québec, Canada.
N
N
Haddjeri
B
B
Seletti
F
F
Gilbert
C
C
de Montigny
P
P
Blier
D018712:Analgesics, Non-Narcotic / Q000494:pharmacology*; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000502:physiology; D004594:Electrophysiology; D004878:Ergotamine / Q000494:pharmacology*; D006168:Guinea Pigs; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007031:Hypothalamus / Q000187:drug effects / Q000502:physiology; D008297:Male; D011388:Prolactin / Q000097:blood; D011903:Raphe Nuclei / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000502:physiology; D012701:Serotonin / Q000502:physiology*; D018490:Serotonin Agents / Q000494:pharmacology
D018712:Analgesics, Non-Narcotic; D011985:Receptors, Serotonin; D018490:Serotonin Agents; D012701:Serotonin; D011388:Prolactin; D004878:Ergotamine