title: Effect of a long-term low tryptophan diet on the prolactin responses to the 5-HT1A and 5-HT2C agonists, 8-OH-DPAT and mCPP in the male rat.
abstract: The study was undertaken to assess the long term effects of tryptophan (TRP) depletion through diet on the prolactin (PRL) responses to the serotonin (5-hydroxytryptophan, 5-HT) agonists m-chlorophenyl-piperazine (mCPP) and 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) in the male rat. The low TRP diet caused significant reductions in both plasma total TRP and brain cortical 5-HT content together with a significant increase in the PRL responses to mCPP. In contrast the PRL responses to 8-OH-DPAT in animals on the low TRP diet for 1 week and 6 weeks were similar to control rats. However, a small but significant increase in PRL was observed at 2 min after dosing in the 1-week group. At the same time the 3H-8-OH-DPAT binding parameters, Kd and Bmax, were similar in both control and TRP depleted animals. The results confirm that long-term TRP depletion causes a deficiency of brain TRP and a subsequent reduction of brain 5-HT. This is associated with an enhanced PRL response to mCPP probably resulting from a functional up-regulation of post-synaptic 5-HT2C receptors. The small or transient changes brought about by long-term TRP depletion on post-synaptic 5-HT1A receptors, suggests that these receptors may be less susceptible to 5-HT depleting effects than the 5-HT2C subtype.
authors.affiliation: University of Oxford, Department of Psychiatry Psychopharmacology Unit, Warneford Hospital, UK. michael.franklin@psyc.ox.ac.uk
authors.forename: M
authors.initials: M
authors.lastname: Franklin
authors.forename: R D
authors.initials: RD
authors.lastname: Craven
authors.forename: B
authors.initials: B
authors.lastname: Dowling
authors.forename: G
authors.initials: G
authors.lastname: Campling
authors.forename: J M
authors.initials: JM
authors.lastname: Elliott
authors.forename: P J
authors.initials: PJ
authors.lastname: Cowen
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology*; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D004032:Diet; D008297:Male; D010879:Piperazines / Q000494:pharmacology*; D011388:Prolactin / Q000097:blood*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin / Q000187:drug effects*; D044263:Receptors, Serotonin, 5-HT1; D012701:Serotonin / Q000378:metabolism; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D014364:Tryptophan / Q000172:deficiency*
chemical_list: D010879:Piperazines; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D014364:Tryptophan; D011388:Prolactin; C015068:1-(3-chlorophenyl)piperazine