Role of G(q) protein in behavioral effects of the hallucinogenic drug 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane

Neuropharmacology. 2007 Jun;52(8):1671-7. doi: 10.1016/j.neuropharm.2007.03.013. Epub 2007 Apr 4.


Extensive evidence suggests that 5-HT2 receptors may play a role in mental disorders including schizophrenia. In addition, several studies indicate that G(q)-coupled 5-HT(2A) receptors are likely targets for the initiation of events leading to the hallucinogenic behavior elicited by lysergic acid diethylamide (LSD), (+/-)1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), and related drugs. However, 5-HT(2A) receptors couple to other G proteins in addition to G(q) protein. To evaluate the role of the G(q) signaling pathway in DOI-induced behaviors, we utilized two behavioral models of 5-HT(2A) receptor activation: induction of head-twitches by DOI, a common response to hallucinogenic drugs in rodents, and DOI elicited anxiolytic-like effects in the elevated plus maze. Experimental subjects were genetically modified mice [Galpha(q)(-/-)] in which the G(q) alpha gene was eliminated. Galpha(q)(-/-) mice exhibited a decrease in DOI-induced head-twitches, when compared to wild-type littermates. In addition, the DOI-induced increase in anxiolytic-like behavior was abolished in Galpha(q)(-/-) mice. These results, combined with our finding that DOI-induced FOS expression in the medial prefrontal cortex was also eliminated in Galpha(q)(-/-) mice, suggests a key role for G(q) protein in hallucinogenic drug effects.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Analysis of Variance
  • Animals
  • Behavior, Animal / drug effects*
  • Behavior, Animal / physiology
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism
  • Dose-Response Relationship, Drug
  • GTP-Binding Protein alpha Subunits, Gq-G11 / deficiency
  • GTP-Binding Protein alpha Subunits, Gq-G11 / physiology*
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / genetics
  • Hallucinogens / pharmacology*
  • Head Movements / drug effects
  • Indophenol / analogs & derivatives*
  • Indophenol / pharmacology
  • Male
  • Maze Learning / drug effects
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Oncogene Proteins v-fos / metabolism
  • Radioligand Assay / methods


  • Hallucinogens
  • Oncogene Proteins v-fos
  • dimethoxy-4-indophenyl-2-aminopropane
  • Indophenol
  • GTP-Binding Protein alpha Subunits, Gq-G11