QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (40) Citing Articles via Google Scholar Google Scholar Articles by Stiedl, O. Articles by Ögren, S. O. Search for Related Content PubMed PubMed Citation Articles by Stiedl, O. Articles by Ögren, S. O.

 Previous Article  |  Next Article 

The Journal of Neuroscience, November 15, 2000, 20(22):8515-8527

Involvement of the 5-HT_1A Receptors in Classical Fear Conditioning in C57BL/6J Mice

Oliver Stiedl¹, Ilga Misane², Joachim Spiess¹, and Sven Ove Ögren²

¹ Department of Molecular Neuroendocrinology, Max Planck Institute for Experimental Medicine, D-37075 Goettingen, Germany, and ² Karolinska Institutet, Division of Behavioral Neuroscience, Department of Neuroscience, SE-171 77 Stockholm, Sweden

The present study examined the involvement of the 5-HT_1A receptors in classical fear conditioning using the 5-HT_1A agonist 8-hydroxy-2-(di-n-propyloamino)tetralin hydrobromide (8-OH-DPAT) and the selective "silent" 5-HT_1A receptor antagonist (N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclo-hexane carboxamide trihydrochloride (WAY 100635). The drugs were administered both subcutaneously and bilaterally into the dorsal hippocampus of male C57BL/6J mice. The training was performed in a single trial in which a tone was followed by a footshock. The retention of context- and tone-dependent fear was examined in separate tests conducted either 1 or 24 hr after training. Subcutaneous 8-OH-DPAT (0.1-1.0 mg/kg), when injected before but not after training, caused a dose-dependent impairment of contextual fear in both 1 and 24 hr tests, whereas tone-dependent fear was less affected. Pretraining intrahippocampal injections of 5.0 µg but not 1.0 µg 8-OH-DPAT caused a severe deficit in contextual fear when tested 24 hr after training. When injected both subcutaneously and intrahippocampally, 8-OH-DPAT induced the 5-HT syndrome, indicative of postsynaptic 5-HT_1A receptor activation at the dose ranges that impaired fear conditioning. However, the behavioral changes induced by 8-OH-DPAT at the time of training could not account for inhibitory effects of 8-OH-DPAT on fear conditioning. Neither subcutaneous (0.03 mg/kg) nor intrahippocampal (0.5 µg per mouse) WAY 100635 altered context- or tone-dependent fear. However, subcutaneous WAY 100635 blocked both the 5-HT syndrome and the impairment of fear conditioning induced by subcutaneous or intrahippocampal 8-OH-DPAT. In contrast, intrahippocampal WAY 100635 blocked the impairment caused by intrahippocampal but not subcutaneous 8-OH-DPAT, indicating the involvement of extrahippocampal 5-HT_1A receptors in fear conditioning. It is concluded that the deficits in fear conditioning induced by 8-OH-DPAT are a result of postsynaptic 5-HT_1A receptor activation that interferes with learning processes operating at acquisition but not consolidation. Furthermore, the dorsohippocampal 5-HT_1A receptors play an important but not exclusive role in the limbic circuitry subserving contextual fear conditioning.

Key words: serotonin; presynaptic and postsynaptic 5-HT_1A receptors; dorsal hippocampus; fear conditioning; 8-OH-DPAT; WAY 100635

---

Copyright © 2000 Society for Neuroscience  0270-6474/00/20228515-13$05.00/0

This article has been cited by other articles:

				W. D. Hirst, T. H. Andree, S. Aschmies, W. E. Childers, T. A. Comery, L. A. Dawson, M. Day, I. B. Feingold, S. M. Grauer, B. L. Harrison, et al. Correlating Efficacy in Rodent Cognition Models with in Vivo 5-Hydroxytryptamine1A Receptor Occupancy by a Novel Antagonist, (R)-N-(2-Methyl-(4-indolyl-1-piperazinyl)ethyl)-N-(2-pyridinyl)-cyclohexane Carboxamide (WAY-101405) J. Pharmacol. Exp. Ther., April 1, 2008; 325(1): 134 - 145. [Abstract] [Full Text] [PDF]

				N. Madjid, E. E. Tottie, M. Luttgen, B. Meister, J. Sandin, A. Kuzmin, O. Stiedl, and S. O. Ogren 5-Hydroxytryptamine 1A Receptor Blockade Facilitates Aversive Learning in Mice: Interactions with Cholinergic and Glutamatergic Mechanisms J. Pharmacol. Exp. Ther., February 1, 2006; 316(2): 581 - 591. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help