Effects of 5,7-dihydroxytryptamine on serotonin1 and serotonin2 receptors throughout the rat central nervous system using quantitative autoradiography

Christine T. Fischette, Bruce Nock, Kenneth Renner

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Abstract

The effects of the serotonin neurotoxin 5,7-dihydroxytryptamine (5,7-DHT), on serotonin1 (5-HT1) and 5-HT2 receptors were investigated using the high degree of resolution provided by quantitative autoradiography in an effort to determine the synaptic location of these receptors 5,7-DHT treatment resulted in a decrease in 5-HT1 binding in the dentate gyrus and CA 3c 4 of the anterior hippocampus and in the dorsal raphe nucleus, whereas no changes were observed in the posterior hippocampus nor in many other brain structures. 5-HT2 receptors exhibited no changes in any brain area examined in response to 5,7-DHT treatment, despite over 90% serotonin depletion in most of the forebrain nuclei examined. The results indicate that at least some of the 5-HT1 sites labelled by [3H]5-HT in the hippocampus and dorsal raphe nucleus are presynaptic, whereas 5-HT2 receptors are probably postsynaptic. In addition, the distribution profiles of 5-HT1 and 5-HT2 binding sites were compared in the rat central nervous system at various anatomical levels. 5-HT1 binding sites were identified using [3H]5-HT, while 5-HT2 binding sites were labelled with [3H]ketanserin. Both receptor subtypes displayed distinctly different localization patterns, which, in most cases was the inverse of the other pattern. In the brainstem it is significant that 5-HT2 receptors are concentrated in the facial nucleus and the motor nucleus of the trigeminal nerve, areas known to influence head and facial movement. The serotonin-mediated head-shake response occurs when 5-HT2 receptors are activated. In contrast, 5-HT1 receptors are distributed throughout the brainstem and in specific portions of the spinal cord. These areas are thought to control the serotonin behavioral syndrome and this behavior is 5-HT1A-mediated. All raphe nuclei were devoid of 5-HT2 receptors; only 5-HT1 receptor were found in these nuclei. Correlations with serotonin terminal distribution patterns are discussed. The pattern of 5-HT2 receptor distribution was also compared with the pattern of α1 receptors, using [3H]prazosin in order to determine whether [3H]ketanserin significantly labels α1 receptors. Although some similarities exist, overlap of binding did not occur in other nuclei, indicating that α1 contamination of this system is probably negligible.

Original languageEnglish
Pages (from-to)263-279
Number of pages17
JournalBrain Research
Volume421
Issue number1-2
DOIs
StatePublished - Sep 22 1987

Keywords

  • 5,7-Dihydroxytryptamine (5,7-DHT)
  • Ketanserin
  • Quantitative autoradiography
  • Serotonin receptor
  • Serotonin receptor
  • Serotonin-mediated behavior

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