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

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 lo w TRP diet caused significant reductions in both plasma total TRP and brain cortical 5-HT content together with a significant increase in the PRL resp onses 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 H-3-8-OH-DPAT binding parameters , K-d and B-max were similar in both control and TRP depleted animals. The results confirm that long-term TRP depletion causes a deficiency of brain T RP and a subsequent reduction of brain 5 -HT. This is associated with an en hanced PRL response to mCPP probably resulting from a functional up-regulat ion of post-synaptic 5-HT2c receptors. The small or transient changes broug ht about by long-term TRP depletion on post-synaptic 5-HT1A receptors, sugg ests that these receptors may be less susceptible to 5-HT depleting effects than the 5-HT2c subtype.