Neuronal circuits involved in the anxiolytic effects of the 5-HT1A receptor agonists 8-OH-DPAT ipsapirone and buspirone in the rat.
In rats, the 5-HT1A receptor full agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and the 5-HT1A receptor partial agonists ipsapirone and buspirone dose dependently and completely inhibited shock-induced ultrasonic vocalization after systemic injection and after microinjection into the dorsal raphe nucleus, a brain region rich in somatodendritic 5-HT1A receptors. As compared with injection into the dorsal raphe nucleus, ipsapirone and 8-OH-DPAT were significantly less potent after microinjection into the lateral ventricle or the median raphe nucleus. Depletion of brain 5-HT (5-hydroxytryptamine) by means of 5,7-dihydroxytryptamine or parachlorophenylalanine inhibited ultrasonic vocalization. In lesioned rats, however, ipsapirone (i.p. or dorsal raphe nucleus) and 8-OH-DPAT (dorsal raphe nucleus) retained their ability to inhibit ultrasonic vocalization and, in non-lesioned rats, bilateral injection of ipsapirone, buspirone and 8-OH-DPAT into the dorsal hippocampus and the amygdala - two brain regions rich in postsynaptic 5-HT1A receptors - also inhibited ultrasonic vocalization. In a Geller-Seifter conflict test, i.p. and local injection of 8-OH-DPAT in the dorsal raphe nucleus and the hippocampus selectively enhanced punished responding. It is suggested that both presynaptic and (possibly to a lesser extent) postsynaptic 5-HT1A receptors are involved in the anxiolytic effects of ipsapirone, buspirone, and 8-OH-DPAT.
Schreiber
R
R
Institute for Neubiology, Department of Psychopharmacology, Cologne, Germany.
De Vry
J
J
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000679:Amygdala / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D002065:Buspirone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004597:Electroshock; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D011743:Pyrimidines / Q000494:pharmacology; D011903:Raphe Nuclei / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D014465:Ultrasonics; D014828:Vocalization, Animal / Q000187:drug effects*
D014151:Anti-Anxiety Agents; D011743:Pyrimidines; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; C043077:ipsapirone; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D002065:Buspirone