5-HT1A receptor agonists prevent in rats the yawning and penile erections induced by direct dopamine agonists.
The new compound (+) S-20499, an amino chromane derivative (8[-4[N-(5-methoxychromane-3yl)N-propyl]aminobutyl] azaspiro[4-5] décane-7,9 dione), is a high affinity full 5-HT1A agonist. We have investigated its effects on dopaminergic transmission. (+) S-20499 displayed a 10(-8) M affinity for D2 dopamine (DA) receptors, 100 fold lower than for 5-HT1A receptors. The hypothermic effect of the drug was reversed by haloperidol in mice, suggesting that it behaves as a direct dopamine agonist. However, increasing doses of (+) S-20499 induced neither yawning nor penile erections, which constitute characteristic responses of direct DA agonists administered at low doses. In addition, (+) S-20499 prevented the apomorphine (100 micrograms/kg SC) induced yawning and penile erections. This inhibition appears to result from the stimulation of 5-HT1A receptors since it is an effect shared by both buspirone (from 5 mg/kg) and 8-OH-DPAT (from 0.10 mg/kg). In addition, when rats are treated with the 5-HT1A receptor antagonist tertatolol (2-5 mg/kg; SC), increasing doses of (+) S-20499 elicit the expected yawns and penile erections. It is concluded that the 5-HT1A agonist property opposes to that of D2 dopamine receptor stimulation with regard to yawning and penile erections.
Unité de Neuropsychopharmacologie, U.R.A. 1170 du C.N.R.S., Faculté de Médecine et Pharmacie de Rouen, Saint Etienne du Rouvray, France.
P
P
Simon
B
B
Guardiola
J
J
Bizot-Espiard
P
P
Schiavi
J
J
Costentin
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000634:Aminoquinolines / Q000494:pharmacology; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D002065:Buspirone / Q000494:pharmacology; D002839:Chromans / Q000494:pharmacology*; D015259:Dopamine Agents / Q000494:pharmacology*; D008297:Male; D051379:Mice; D010410:Penile Erection / Q000187:drug effects*; D011412:Propanolamines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism; D011985:Receptors, Serotonin / Q000187:drug effects*; D013141:Spiro Compounds / Q000494:pharmacology*; D013876:Thiophenes; D015000:Yawning / Q000187:drug effects*
D000319:Adrenergic beta-Antagonists; D000634:Aminoquinolines; D002839:Chromans; D015259:Dopamine Agents; D011412:Propanolamines; D017448:Receptors, Dopamine D2; D011985:Receptors, Serotonin; D013141:Spiro Compounds; D013876:Thiophenes; C066809:Sandoz 205-501; C075319:alnespirone; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C005632:tertatolol; D002065:Buspirone