Role of G(q) protein in behavioral effects of the hallucinogenic drug 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane.
Efrain E. Garcia, Randy L Smith, Elaine Sanders‐bush
Neuropharmacology June 2007 DOI: 10.1016/j.neuropharm.2007.03.013 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort Peer reviewed |
|---|---|
| Population | Genetically modified mice (Galpha(q)(-/-)) and wild-type littermates |
| Intervention | DOI |
| Measures | head-twitch response, elevated plus maze, FOS expression |
| Key findings | Galpha(q)(-/-) mice exhibited a decrease in DOI-induced head-twitches compared to wild-type littermates, and the DOI-induced increase in anxiolytic-like behavior was abolished. DOI-induced FOS expression in the medial prefrontal cortex was also eliminated, suggesting a key role for G(q) protein in hallucinogenic drug effects. |
Abstract
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.