Direct injection of 5-HT(2A) receptor agonists into the medial prefrontal cortex produces a head-twitch response in rats

David L. Willins*, Herbert Y. Meltzer

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

190 Scopus citations

Abstract

The serotonin (5-HT)(2A/2C) agonist 1-(2,5-dimethoxy-4-iodophenyl)-2- aminopropane (DOI), the 5-HT(2C) agonist 6-chloro-2-[1-piperazinyl]-pyrazine and the 5-HT(2A) partial agonist m-chloro-phenylpiperazine (mCPP) were injected bilaterally into the medial prefrontal cortex of male rats. DOI and mCPP, but not 6-chloro-2-[1-piperazinly]-pyrazine, elicited a dose-dependent head-twitch response (HTR). DOI-induced HTR had an ED50 of 12.8 nmoles/0.5 μl/side and was inhibited by the 5-HT(2A) antagonists ketanserin and MDL 100,907 but was not blocked by pretreatment with the selective 5-HT(2C/2B) antagonist SDZ SER 082. The HTR to mCPP demonstrated a bell-shaped dose- response curve with an ED50 of 1.5 nmoles/0.5 μl/side and a peak effect after 3 nmoles/side. The response to mCPP was greatly diminished by both ketanserin and MDL 100,907 and was partially reversed by SDZ SER 082. These findings suggest that the HTR produced by the direct injection of serotonergic agonists into the medial prefrontal cortex is, in part, mediated by the activation of 5-HT(2A) receptors. Pretreatment of rats with the 5- HT(1A) agonist (±)-8-hydroxy-dipropylaminotetralin hydrobromide inhibited the HTR to DOI. This is consistent with other evidence that suggests a functional antagonism between 5-HT(1A) and 5-HT(2A) receptor activation. The HTR to DOI was potentiated by the novel 5-HT(1A) selective antagonist WAY 100,635, which suggests that 5-HT(1A) receptors tonically regulate this behavioral response to stimulation of cortical 5-HT(2A) receptors.

Original languageEnglish (US)
Pages (from-to)699-706
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume282
Issue number2
StatePublished - Aug 1 1997

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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