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Extracellular serotonin in the prefrontal cortex is limited through terminal 5-HT(1B) autoreceptors: a microdialysis study in knockout mice.
Psychopharmacology (Berl). 2002 Aug; 162(4):419-24.P

Abstract

RATIONALE

Serotonin (5-HT) autoreceptors regulate extracellular 5-HT levels and have been suggested to limit the effects of acute treatment with selective serotonin reuptake inhibitors (SSRIs).

OBJECTIVES

The role of terminal 5-HT(1B) autoreceptors was assessed by comparing the effects of a SSRI on extracellular 5-HT in wild-type and 5-HT(1B) receptor knockout (KO) mice and by using a 5-HT(1B) receptor antagonist. Since systemic SSRI administration also activates somatodendritic 5-HT(1A) autoreceptors, a SSRI was administered locally to study the role of terminal 5-HT(1B) autoreceptors.

METHODS

In vivo microdialysis in wild-type and 5-HT(1B) receptor KO mice was used to study the effects of the 5-HT(1B) receptor agonist CP93129 (1 micro M), the SSRI fluvoxamine (0.3 micro M and 1.0 micro M) and the 5-HT(1B) receptor antagonist NAS-181 (1 micro M) on extracellular 5-HT in the medial prefrontal cortex.

RESULTS

The 5-HT increase induced by local SSRI administration was augmented in 5-HT(1B) KO mice relative to wild-type mice and was augmented by simultaneous administration of a 5-HT(1B) receptor antagonist in the latter genotype. Basal 5-HT levels did not differ between the two genotypes. Activation of 5-HT(1B) receptors by CP93129 decreased extracellular 5-HT, whereas 5-HT levels in wild-type mice were not affected by the 5-HT(1B) receptor antagonist NAS-181. In 5-HT(1B) KO mice, NAS-181 did not affect extracellular 5-HT and did not further increase the effect of fluvoxamine, showing that NAS-181 is a selective 5-HT(1B) receptor antagonist. The greater increase in 5-HT levels following combined administration of a SSRI with NAS-181 in wild-type mice, relative to 5-HT(1B) KO mice, suggests possible adaptive changes in the KO mice.

CONCLUSIONS

The present study shows that terminal 5-HT(1B) autoreceptors play a significant role in the regulation of 5-HT release in the prefrontal cortex.

Authors+Show Affiliations

Department of Psychiatry, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands. L.deGroote@psych.azu.nlNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

12172696

Citation

de Groote, Lotte, et al. "Extracellular Serotonin in the Prefrontal Cortex Is Limited Through Terminal 5-HT(1B) Autoreceptors: a Microdialysis Study in Knockout Mice." Psychopharmacology, vol. 162, no. 4, 2002, pp. 419-24.
de Groote L, Olivier B, Westenberg HG. Extracellular serotonin in the prefrontal cortex is limited through terminal 5-HT(1B) autoreceptors: a microdialysis study in knockout mice. Psychopharmacology (Berl). 2002;162(4):419-24.
de Groote, L., Olivier, B., & Westenberg, H. G. (2002). Extracellular serotonin in the prefrontal cortex is limited through terminal 5-HT(1B) autoreceptors: a microdialysis study in knockout mice. Psychopharmacology, 162(4), 419-24.
de Groote L, Olivier B, Westenberg HG. Extracellular Serotonin in the Prefrontal Cortex Is Limited Through Terminal 5-HT(1B) Autoreceptors: a Microdialysis Study in Knockout Mice. Psychopharmacology (Berl). 2002;162(4):419-24. PubMed PMID: 12172696.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Extracellular serotonin in the prefrontal cortex is limited through terminal 5-HT(1B) autoreceptors: a microdialysis study in knockout mice. AU - de Groote,Lotte, AU - Olivier,Berend, AU - Westenberg,Herman G M, Y1 - 2002/06/14/ PY - 2002/01/10/received PY - 2002/03/25/accepted PY - 2002/8/13/pubmed PY - 2003/1/8/medline PY - 2002/8/13/entrez SP - 419 EP - 24 JF - Psychopharmacology JO - Psychopharmacology (Berl) VL - 162 IS - 4 N2 - RATIONALE: Serotonin (5-HT) autoreceptors regulate extracellular 5-HT levels and have been suggested to limit the effects of acute treatment with selective serotonin reuptake inhibitors (SSRIs). OBJECTIVES: The role of terminal 5-HT(1B) autoreceptors was assessed by comparing the effects of a SSRI on extracellular 5-HT in wild-type and 5-HT(1B) receptor knockout (KO) mice and by using a 5-HT(1B) receptor antagonist. Since systemic SSRI administration also activates somatodendritic 5-HT(1A) autoreceptors, a SSRI was administered locally to study the role of terminal 5-HT(1B) autoreceptors. METHODS: In vivo microdialysis in wild-type and 5-HT(1B) receptor KO mice was used to study the effects of the 5-HT(1B) receptor agonist CP93129 (1 micro M), the SSRI fluvoxamine (0.3 micro M and 1.0 micro M) and the 5-HT(1B) receptor antagonist NAS-181 (1 micro M) on extracellular 5-HT in the medial prefrontal cortex. RESULTS: The 5-HT increase induced by local SSRI administration was augmented in 5-HT(1B) KO mice relative to wild-type mice and was augmented by simultaneous administration of a 5-HT(1B) receptor antagonist in the latter genotype. Basal 5-HT levels did not differ between the two genotypes. Activation of 5-HT(1B) receptors by CP93129 decreased extracellular 5-HT, whereas 5-HT levels in wild-type mice were not affected by the 5-HT(1B) receptor antagonist NAS-181. In 5-HT(1B) KO mice, NAS-181 did not affect extracellular 5-HT and did not further increase the effect of fluvoxamine, showing that NAS-181 is a selective 5-HT(1B) receptor antagonist. The greater increase in 5-HT levels following combined administration of a SSRI with NAS-181 in wild-type mice, relative to 5-HT(1B) KO mice, suggests possible adaptive changes in the KO mice. CONCLUSIONS: The present study shows that terminal 5-HT(1B) autoreceptors play a significant role in the regulation of 5-HT release in the prefrontal cortex. SN - 0033-3158 UR - https://www.unboundmedicine.com/medline/citation/12172696/Extracellular_serotonin_in_the_prefrontal_cortex_is_limited_through_terminal_5_HT_1B__autoreceptors:_a_microdialysis_study_in_knockout_mice_ L2 - https://dx.doi.org/10.1007/s00213-002-1117-z DB - PRIME DP - Unbound Medicine ER -