L-5-HTP facilitates the electrically stimulated flexor reflex in pithed rats: evidence for 5-HT2-receptor mediation.
Different serotonin (5-HT) receptor agonists were tested on the electrically stimulated flexor reflex in pithed rats. The 5-HT2 receptor agonist, (1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane) [+/-)DOI), the mixed 5-HT1/5-HT2 receptor agonist, quipazine, and the 5-HT precursor, l-5-HTP, showed agonistic activity upon intravenous injection while 5-HT was without effect. A combination of the peripheral decarboxylase inhibitor, Ro 4-4602 (benzerazide), the specific 5-HT-uptake inhibitor, citalopram, and l-5-HTP induced a prolonged (greater than 3 h) increase of the flexor reflex in pithed rats. Different compounds were tested for an inhibitory effect against this l-5-HTP-induced flexor reflex. The 5-HT2 antagonists (ketanserin, methergoline and methiothepin) were potent antagonists. (-)Alprenolol (5-HT1A and 5-HT1B receptor antagonist) and the 5-HT3-receptor antagonist, ICS 205-930, were without an antagonistic effect. The inhibitory potencies in the reflex model (l-5-HTP, citalopram and Ro 4-4602) were significantly correlated (r = 0.83, P less than 0.01, r2 = 0.69) with the potencies to inhibit l-5-HTP-induced head twitches and quipazine-induced head twitches (r = 0.81, P less than 0.01, r2 = 0.66). There was less correlation (r = 0.75, P less than 0.01, r2 = 0.56) with the affinities for 5-HT2 receptors in vitro. There was no significant correlation between inhibitory potencies in the reflex model and affinities for dopamine (DA) D-2 receptors or alpha 1-adrenoceptors (r2 = 0.13 and 0.14, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
Skarsfeldt
T
T
Pharmacological Research, H. Lundbeck A/S, Copenhagen-Valby, Denmark.
Arnt
J
J
Hyttel
J
J
D006916:5-Hydroxytryptophan / Q000494:pharmacology*; D000662:Amphetamines / Q000494:pharmacology; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D001545:Benserazide / Q000494:pharmacology; D015283:Citalopram / Q000494:pharmacology; D003655:Decerebrate State; D004558:Electric Stimulation; D008297:Male; D011814:Quipazine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism; D011954:Receptors, Dopamine / Q000187:drug effects; D011985:Receptors, Serotonin / Q000187:drug effects*; D012018:Reflex / Q000187:drug effects*; D012701:Serotonin / Q000502:physiology; D012702:Serotonin Antagonists / Q000494:pharmacology
D000662:Amphetamines; D014150:Antipsychotic Agents; D011942:Receptors, Adrenergic, alpha; D011954:Receptors, Dopamine; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D015283:Citalopram; D012701:Serotonin; D011814:Quipazine; D001545:Benserazide; D006916:5-Hydroxytryptophan; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine