Effect of gepirone and ipsapirone on the stimulated and unstimulated secretion of prolactin in the rat.
Previous studies have demonstrated that the 5-hydroxytryptamine1A (5-HT1A) agonist buspirone stimulated rat prolactin (PRL) secretion. Administration of the 5-HT1A agonists gepirone (GEP) or ipsapirone (IPS) s.c. in doses from 1 to 10 mg/kg had no effect on PRL secretion in male rats. However, pretreatment with GEP (10 mg/kg) or IPS (10 mg/kg) significantly attenuated the increase in serum PRL concentration elicited by the 5-HT agonists 5-methoxy-N,N-dimethyltryptamine or 6-chloro-2-(1-piperazinyl)-pyrazine (MK-212). To determine whether the inhibitory effect of GEP or IPS was related to a serotonergic mechanism or a more general inhibitory effect on PRL secretion, the ability of GEP and IPS to inhibit the haloperidol- or alpha-methyl-p-tyrosine-induced increase in PRL secretion was studied. GEP (1, 3 and 10 mg/kg) and IPS (10 mg/kg) inhibited the increase in PRL secretion produced by either haloperidol (0.25 mg/kg) or alpha-methyl-p-tyrosine (75 mg/kg). Furthermore, GEP produced a concentration-dependent inhibition of PRL secretion from anterior pituitary tissue incubated in vitro. The inhibitory effect of GEP was comparable to that of dopamine in this system. Moreover, haloperidol blocked completely the GEP-mediated suppression of PRL secretion in this preparation. These data suggest agonist properties of both GEP and IPS at D2 dopamine receptors. In light of other evidence that GEP has D2 antagonist effects in vivo, we hypothesize that GEP and perhaps IPS are partial dopamine agonists which may contribute to their antianxiety and/or antidepressant properties.
Nash
J F
JF
Department of Psychiatry, School of Medicine, Case Western Reserve University, Cleveland, Ohio.
Meltzer
H Y
HY
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D004558:Electric Stimulation; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D008732:Methoxydimethyltryptamines / Q000494:pharmacology; D008781:Methyltyrosines / Q000494:pharmacology; D011388:Prolactin / Q000378:metabolism*; D011719:Pyrazines / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D019805:alpha-Methyltyrosine
D014151:Anti-Anxiety Agents; D008732:Methoxydimethyltryptamines; D008781:Methyltyrosines; D011719:Pyrazines; D011743:Pyrimidines; D011954:Receptors, Dopamine; D013764:Tetrahydronaphthalenes; C014896:6-chloro-2-(1-piperazinyl)pyrazine; D019805:alpha-Methyltyrosine; C043077:ipsapirone; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D011388:Prolactin; D006220:Haloperidol; C039979:gepirone