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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

University of Oxford Department of Psychiatry Psychopharmacology Unit, Warneford Hospital, Oxford OX3 7JX

R. D. Craven

Biology and Molecular Sciences, Oxford-Brookes University, Oxford OX3 OBP

B. Dowling

G. Campling

University of Oxford Department of Psychiatry Psychopharmacology Unit, Warneford Hospital, Oxford OX3 7JX

J. M. Elliott

University of Oxford Clinical Pharmacology, Radcliffe Infirmary, Oxford OX2 6HE, UK

P. J. Cowen

University of Oxford Department of Psychiatry Psychopharmacology Unit, Warneford Hospital, Oxford OX3 7JX

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 1week 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, K_d and B_max, were similar in both control and TRP depleted animals. The results conform 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-HT_2Creceptors. The small or transient changes brought about by long-term TRP depletion on post-synaptic 5-HT_1Areceptors, suggests that these receptors may be less susceptible to 5-HT depleting effects than the 5-HT_2Csubtype.

Key Words: diet • 5-HT • mCPP • 8-OH-DPAT • prolactin • tryptophan

Journal of Psychopharmacology, Vol. 13, No. 1, 58-63 (1999)
DOI: 10.1177/026988119901300107


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