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Inhibition of hippocampal 5-HT synthesis by fluoxetine and paroxetine: evidence for the involvement of both 5-HT1A and 5-HT1B/D autoreceptors.
Synapse. 1999 Jan; 31(1):13-9.S

Abstract

Hippocampal serotonin (5-hydroxytryptamine, 5-HT) synthesis, as determined by the accumulation of 5-hydroxytryptophan (5-HTP) following inhibition of L-aromatic amino acid decarboxylase with NSD 1015, was inhibited by systemic administration of the selective serotonin reuptake inhibitors fluoxetine (10 mg/kg i.p.) and paroxetine (3 mg/kg i.p.). Pretreatment of rats with the selective 5-HT1A receptor antagonist WAY 100635 for a period of 7 days using subcutaneously implanted osmotic minipumps (1 mg/kg/day) was sufficient to block the inhibition of 5-HT synthesis following the 5-HT 1A receptor agonist 8-OH-DPAT (0.3 mg/kg s.c.), but failed to inhibit the decrease of hippocampal 5-HT synthesis by fluoxetine (10 mg/kg i.p.) or paroxetine (3 mg/kg i.p.). Similarly, pretreatment of rats with GR 127935 (5 mg/kg i.p.), an antagonist with high affinity for 5-HT1B/D receptors, blocked the reduction of hippocampal 5-HT synthesis following the 5-HT receptor agonist TFMPP (3 mg/kg s.c.) without affecting the reduction of hippocampal 5-HT synthesis by either fluoxetine or paroxetine. In contrast, pretreatment with WAY 100635 (1 mg/kg/day, for 7 days s.c. in osmotic minipumps) in combination with GR 127935 (5 mg/kg i.p.) significantly attenuated the decrease of hippocampal 5-HT synthesis by both fluoxetine and paroxetine. These results indicate that both 5-HT1A and 5-HT1B/1D receptors, which function in the rat as inhibitory somatodendritic and nerve terminal autoreceptors, independently regulate hippocampal 5-HT synthesis and must be simultaneously blocked to prevent the inhibition of 5-HT synthesis by selective serotonin reuptake inhibitors which increase 5-HT availability at both nerve terminals in hippocampus and 5-HT cell bodies in the raphe nuclei.

Authors+Show Affiliations

Merck Sharp and Dohme, Neuroscience Research Centre, Harlow Essex, UK.No affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

10025679

Citation

Barton, C L., and P H. Hutson. "Inhibition of Hippocampal 5-HT Synthesis By Fluoxetine and Paroxetine: Evidence for the Involvement of Both 5-HT1A and 5-HT1B/D Autoreceptors." Synapse (New York, N.Y.), vol. 31, no. 1, 1999, pp. 13-9.
Barton CL, Hutson PH. Inhibition of hippocampal 5-HT synthesis by fluoxetine and paroxetine: evidence for the involvement of both 5-HT1A and 5-HT1B/D autoreceptors. Synapse. 1999;31(1):13-9.
Barton, C. L., & Hutson, P. H. (1999). Inhibition of hippocampal 5-HT synthesis by fluoxetine and paroxetine: evidence for the involvement of both 5-HT1A and 5-HT1B/D autoreceptors. Synapse (New York, N.Y.), 31(1), 13-9.
Barton CL, Hutson PH. Inhibition of Hippocampal 5-HT Synthesis By Fluoxetine and Paroxetine: Evidence for the Involvement of Both 5-HT1A and 5-HT1B/D Autoreceptors. Synapse. 1999;31(1):13-9. PubMed PMID: 10025679.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inhibition of hippocampal 5-HT synthesis by fluoxetine and paroxetine: evidence for the involvement of both 5-HT1A and 5-HT1B/D autoreceptors. AU - Barton,C L, AU - Hutson,P H, PY - 1999/2/20/pubmed PY - 2000/6/20/medline PY - 1999/2/20/entrez SP - 13 EP - 9 JF - Synapse (New York, N.Y.) JO - Synapse VL - 31 IS - 1 N2 - Hippocampal serotonin (5-hydroxytryptamine, 5-HT) synthesis, as determined by the accumulation of 5-hydroxytryptophan (5-HTP) following inhibition of L-aromatic amino acid decarboxylase with NSD 1015, was inhibited by systemic administration of the selective serotonin reuptake inhibitors fluoxetine (10 mg/kg i.p.) and paroxetine (3 mg/kg i.p.). Pretreatment of rats with the selective 5-HT1A receptor antagonist WAY 100635 for a period of 7 days using subcutaneously implanted osmotic minipumps (1 mg/kg/day) was sufficient to block the inhibition of 5-HT synthesis following the 5-HT 1A receptor agonist 8-OH-DPAT (0.3 mg/kg s.c.), but failed to inhibit the decrease of hippocampal 5-HT synthesis by fluoxetine (10 mg/kg i.p.) or paroxetine (3 mg/kg i.p.). Similarly, pretreatment of rats with GR 127935 (5 mg/kg i.p.), an antagonist with high affinity for 5-HT1B/D receptors, blocked the reduction of hippocampal 5-HT synthesis following the 5-HT receptor agonist TFMPP (3 mg/kg s.c.) without affecting the reduction of hippocampal 5-HT synthesis by either fluoxetine or paroxetine. In contrast, pretreatment with WAY 100635 (1 mg/kg/day, for 7 days s.c. in osmotic minipumps) in combination with GR 127935 (5 mg/kg i.p.) significantly attenuated the decrease of hippocampal 5-HT synthesis by both fluoxetine and paroxetine. These results indicate that both 5-HT1A and 5-HT1B/1D receptors, which function in the rat as inhibitory somatodendritic and nerve terminal autoreceptors, independently regulate hippocampal 5-HT synthesis and must be simultaneously blocked to prevent the inhibition of 5-HT synthesis by selective serotonin reuptake inhibitors which increase 5-HT availability at both nerve terminals in hippocampus and 5-HT cell bodies in the raphe nuclei. SN - 0887-4476 UR - https://www.unboundmedicine.com/medline/citation/10025679/Inhibition_of_hippocampal_5_HT_synthesis_by_fluoxetine_and_paroxetine:_evidence_for_the_involvement_of_both_5_HT1A_and_5_HT1B/D_autoreceptors_ L2 - https://doi.org/10.1002/(SICI)1098-2396(199901)31:1<13::AID-SYN3>3.0.CO;2-Y DB - PRIME DP - Unbound Medicine ER -