Serotonin autoreceptor function
and antidepressant drug action

by
Hjorth S, Bengtsson HJ, Kullberg A,
Carlzon D, Peilot H, Auerbach SB
Institute for Physiology and Pharmacology,
Department of Pharmacology,
Goteborg University,
Sweden.
stephan.hjorth@pharm.gu.se
J Psychopharmacol 2000 Jun; 14(2):177-85


ABSTRACT

This article briefly summarizes, within the context of a brief review of the relevant literature, the outcome of our recent rat microdialysis studies on (1) the relative importance of serotonin (5-HT)1A versus 5-HT1B autoreceptors in the mechanism of action of 5-HT reuptake blocking agents, including putative regional differences in this regard, and (2) autoreceptor responsiveness following chronic SSRI administration. First, our data are consistent with the primacy of 5-HT1A autoreceptors in restraining the elevation of 5-HT levels induced by SSRIs, whereas nerve terminal 5-HT1B autoreceptors appear to have an accessory role in this regard. Second, there is an important interplay between cell body and nerve terminal 5-HT autoreceptors, and recent findings suggest that this interplay may potentially be exploited to obtain regionally preferential effects on 5-HT neurotransmission in the central nervous system, even upon systemic drug administration. In particular, emerging data suggest that somatodendritic 5-HT1A autoreceptor- and nerve terminal 5-HT1B autoreceptor-mediated feedback may be relatively more important in the control of 5-HT output in dorsal raphe-frontal cortex and median raphe-dorsal hippocampus systems, respectively. Third, 5-HT autoreceptors evidently retain the capability to limit the 5-HT transmission-promoting effect of SSRIs after chronic treatment. Thus, although the responsiveness of these sites is probably somewhat reduced, residual autoreceptor capacity still remains an effective restraint on large increases in extracellular 5-HT, even after prolonged treatment. If a further increase in extracellular 5-HT is crucial to the remission of depression in patients responding only partially to prolonged administration of antidepressants, then sustained adjunctive treatment with autoreceptor-blocking drugs may consequently prove useful in the long term.
P11
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Serotonin
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Anpirtoline
Melancholia
SSRI spectrum
SSRI mechanisms
Future anxiolytics
MDMA neurotoxicity
SSRIs and microbes
21C antidepressants
Serotonin control genes
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SNaRIs, NaSSAs, and NaRIs
Serotonin and romantic lovers
5-HT1a agonists as antidepressants
The monoamine theory of depression
Fluoxetine (Prozac): 10th Anniversary
5-HT1b inverse agonists as antidepressants
5-HT7 receptor antagonists as antidepressants


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