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.
Simon
P
P
Unité de Neuropsychopharmacologie, U.R.A. 1170 du C.N.R.S., Faculté de Médecine et Pharmacie de Rouen, Saint Etienne du Rouvray, France.
Guardiola
B
B
Bizot-Espiard
J
J
Schiavi
P
P
Costentin
J
J
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