Genomic responses to 5-HT1a or 5-HT2a2c receptor activation is differentially regulated in four regions of rat brain

Tilakaratne, Nanda; Friedman, Eitan A.

doi:10.1016/0014-2999(96)00233-6

Cited by 45 publications

(17 citation statements)

References 19 publications

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“…These results support the view that serotonergic activation of the 5-HT 2A Rs provides an important modulatory influence on circuits engaged during extinction learning (Zhang et al 2013). It is also possible that 5-HT 2A Rs are involved in hippocampal cytoskeletal protein (Arc) increase induced by BLA activation (McIntyre et al 2005) since early evidence has shown that DOI modulates activation of hippocampal immediate early genes (Tilakaratne and Friedman 1996). Furthermore, 5-HT 2A R might mediate BLA-induced adult hippocampal neurogenesis in fear context-specific activation (Kirby et al 2012).…”

Section: Role Of 5-ht 2a Rs On Amygdala/hippocampus Interaction In Emsupporting

confidence: 79%

Functional anatomy of 5-HT2A receptors in the amygdala and hippocampal complex: relevance to memory functions

Bombardi

Giovanni

2013

Exp Brain Res

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Section: Role Of 5-ht 2a Rs On Amygdala/hippocampus Interaction In Emsupporting

confidence: 79%

Functional anatomy of 5-HT2A receptors in the amygdala and hippocampal complex: relevance to memory functions

Bombardi

Giovanni

2013

Exp Brain Res

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“…Consistent with this interpretation, antisense inhibition of arc expression leads to impairment of the maintenance phase, but not the induction, of long-term potentiation (Guzowski et al 2000). LSD produced a robust fivefold increase in arc expression in the prefrontal cortex, similar to that seen with the hallucinogenic drug 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (Pei et al 2000;Tilakaratne and Friedman 1996). Arc gene expression was not increased in the hippocampus by LSD and was not detectable in the midbrain region.…”

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confidence: 70%

A Single Dose of Lysergic Acid Diethylamide Influences Gene Expression Patterns within the Mammalian Brain

Nichols

Sanders‐Bush

2002

Neuropsychopharmacology

139

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Hallucinogenic drugs such as lysergic acid diethylamide (LSD) have profound effects on humans including INTRODUCTIONLysergic acid diethylamide (LSD) is an hallucinogenic drug that transiently but powerfully alters human perception, behavior, and mood at extremely low doses. Certain aspects of the behavior elicited by acute doses of LSD closely resemble symptoms of mental disorders such as schizophrenia (Breier 1995). Despite extensive research over the past four decades, the mechanism of action of hallucinogenic drugs still largely remains a mystery. The behavioral effects of LSD are believed to arise in part from agonist activity at the 5-HT 2A , 5-HT 2C , and 5-HT 1A receptor subtypes (Burris et al. 1991; KrebsThomson et al. 1998;Titeler et al. 1988), but if, and how, these interactions affect cognitive functions remains unknown. In addition to actions at serotonin receptors, LSD has high affinity for dopamine receptors and has been shown to act as an agonist at these receptors (Giacomelli et al. 1998;Watts et al. 1995). Because LSD is a unique ligand that can simultaneously bind to serotonin and dopamine receptor subtypes implicated in both normal and abnormal human behaviors, it is an excellent tool for probing the biochemical basis for behavior.Simply increasing brain levels of serotonin, however, does not produce hallucinogenic effects. Recent work has demonstrated that while LSD binds to the same re- NO . 5 LSD-influenced Gene Expression 635 ceptor sites as the endogenous ligand serotonin, it has the capacity to activate different intracellular signaling cascades (Backstrom et al. 1999). Because intracellular signaling cascades influence gene expression, LSDinduced signaling events within cells may inappropriately alter gene expression, which in turn may lead to changes in the physiological status of the neurons, ultimately altering the processes of cognition. Certain behavioral effects of LSD resemble paranoid schizophrenia in humans. This particular subset of mood alterations occurs within the "second phase . . . of the LSD experience" as defined by Freedman, and may be specific for LSD (Freedman 1984). These delayed "second phase" effects could result from transient changes in gene expression. Thus, identifying and characterizing these genes could prove to be important in understanding mechanisms underlying how hallucinogens such as LSD alter behavior. In addition, understanding these mechanisms may lead to the identification of novel therapeutic targets for treatment of mental disorders.We took a broad approach to investigating and identifying genes that are altered by an acute dose of LSD in the mammalian brain. First, we investigated the expression of the mRNAs of the 5-HT receptor subtypes thought to mediate hallucinogenic effects in animal models (5-HT 1A,2A,2C ), as well as, specific gene expression of immediate early genes predicted to be affected by LSD. Next, we performed a DNA microarray screen to identify gene expression influenced by LSD at a more global level. For each gene identified,...

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“…Acute administration of DOI elicits a 5-HT 2A receptor-dependent induction of the immediate early gene c-fos and its protein FOS in the rat cortex (Leslie et al, 1993;Scruggs et al, 2000;Tilakaratne and Friedman, 1996). In mouse behavioral assays, DOI has been shown to exhibit anxiolytic-like properties in anxiety paradigms such as the four plates test and the elevated plus maze (Nic Dhonnchadha et al, 2003;Onaivi et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

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

2007

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SUMMARYExtensive 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 [Gα q (−/−)] in which the G q alpha gene was eliminated. Gα 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 Gα q (−/−) mice. These results, combined with our finding that DOI-induced FOS expression in the medial prefrontal cortex was also eliminated in Gα q (−/−) mice, suggests a key role for G q protein in hallucinogenic drug effects.

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Genomic responses to 5-HT1a or 5-HT2a2c receptor activation is differentially regulated in four regions of rat brain

Cited by 45 publications

References 19 publications

Functional anatomy of 5-HT2A receptors in the amygdala and hippocampal complex: relevance to memory functions

Functional anatomy of 5-HT2A receptors in the amygdala and hippocampal complex: relevance to memory functions

A Single Dose of Lysergic Acid Diethylamide Influences Gene Expression Patterns within the Mammalian Brain

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

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