Abstract
Little is currently known regarding the electrophysiological response elicited by 5-hydroxytryptamine-7 (5-HT7) receptor stimulation in the brain. Previous anatomical studies have shown that the anterior thalamus expresses a high density of 5-HT7receptors. Therefore, we used whole-cell recording techniques in the in vitro brain slices to examine the effects of serotonin on neurons of the anterodorsal nucleus of the thalamus (ADn). Bath application of 5-HT induces a large membrane depolarization and inward current in neurons of the ADn. Since these cells expressed 5-HT7receptor mRNA, as determined by single-cell reverse transcriptase-polymerase chain reaction, we pharmacologically characterized the 5-HT receptor mediating this response. We found that the 5-HT1 and 5-HT7 agonists 5-carboxamidotryptamine (5-CT) and 5-methoxytryptamine mimicked the response to 5-HT, whereas the 5-HT2 agonist 2,5-dimethoxy-4-iodoamphetamine did not. Consistent with the involvement of a 5-HT7 receptor, 5-CT was approximately 18 times more potent than 5-HT. Furthermore, administration of the 5-HT1A and 5-HT7 agonist 8-hydroxydipropylaminotetralin mimicked and antagonized the effect of serotonin, suggesting it acted as a partial agonist. To determine if either the 5-HT1 or 5-HT7 receptor mediated the 5-HT-induced inward current, we used antagonists. We found that the 5-HT7 ligands ritanserin, methylsergide, LSD, and mesulergine could inhibit the 5-HT-induced inward current, whereas the 5-HT1 antagonist cyanopindolol had no effect. The pA2 value determined for mesulergine closely approximated that expected for a 5-HT7 receptor. Finally, we found that bath application of the selective antagonist SB-269770 blocks the 5-HT-induced inward current. These results identify the receptor mediating the serotonin-induced membrane depolarization in the ADn as the 5-HT7 subtype.
Footnotes
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Send reprint requests to: Dr. Rodrigo Andrade, Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, 2309 Scott Hall, Detroit, MI 48201. E-mail:randrade{at}med.wayne.edu
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This work was supported by Grant MH43985 from the National Institute of Mental Health. This study was also supported in part by a research grant (Joe Young, Sr.) from the State of Michigan.
- Abbreviations:
- 5-HT
- 5-hydroxytryptamine
- 5-CT
- 5-carboxamidotryptamine
- 5-MeOT
- 5-methoxytryptamine
- 8-OHDPAT
- 8-hydroxydipropylaminotetralin
- DOI
- 2,5-dimethoxy-4-iodoamphetamine
- ADn
- anterodorsal nucleus of the thalamus
- BAPTA
- 1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid
- RT-PCR
- reverse transcriptase-polymerase chain reaction
- LSD
- lysergic acid diethylamide
- bp
- base pair
- EC50
- effective concentration of 50%
- Received September 14, 2000.
- Accepted December 20, 2000.
- The American Society for Pharmacology and Experimental Therapeutics
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