Inhibition of 5-hydroxytryptamine neuronal activity by the 5-HT agonist, DOI

Garratt, Jeni C.; Kidd, Emma Jane; Wright, Ian K.; Marsden, C.A.

doi:10.1016/0014-2999(91)90499-g

Cited by 60 publications

(19 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Hitchcock et al (1997) reported that the 5HT 2A receptor agonist DOI disrupted LI when given in preexposure only (but not in both stages) and this disruption was reversed by the 5HT 2A antagonist M100907 as well as by antipsychotics possessing 5HT 2A antagonist action, clozapine and risperidone, and haloperidol. As pointed out by Moser et al (1996Moser et al ( , 2000, while this result seems perplexing given that 5HT 2A antagonists and antipsychotics possessing 5HT 2A antagonist action also disrupt LI when given in pre-exposure (Cassaday et al 1993a;Shadach et al 2000), it can be explained by findings that systemic administration of DOI inhibits the neuronal firing of serotonergic neurons, and reduces 5HT release in the frontal cortex (Wright et al 1990;Martin-Ruiz et al 2001), although the latter effect is not consistently reversed by selective 5HT 2A antagonists (Garratt et al 1991;Martin-Ruiz et al 2001). DOI may concomitantly activate 5HT 2A receptors and increase 5HT release in the prefrontal cortex (Marek and Aghajanin 1998;Aghajanian and Marek 2000;Martin-Ruiz et al 2001), possibly disrupting the balance between the inhibitory and excitotry inputs to the prefrontal cortex.…”

Section: The Serotonergic Systemmentioning

confidence: 80%

The "two-headed" latent inhibition model of schizophrenia: modeling positive and negative symptoms and their treatment

2003

View full text Add to dashboard Cite

Different drug and lesion manipulations produce two poles of abnormality in LI, namely, disrupted LI under conditions which lead to LI in normal rats, and abnormally persistent LI under conditions which disrupt it in normal rats. Disrupted and persistent LI are differentially responsive to APDs, with the former reversed by both typical and atypical APDs and the latter selectively reversed by atypical APDs. It is suggested that this "two-headed LI model" mimics two extremes of deficient cognitive switching seen in schizophrenia, excessive and retarded switching between associations, mediated by dysfunction of different brain circuitries, and can serve to model positive symptoms of schizophrenia and typical antipsychotic action, as well as negative symptoms of schizophrenia and atypical antipsychotic action.

show abstract

Section: The Serotonergic Systemmentioning

confidence: 80%

The "two-headed" latent inhibition model of schizophrenia: modeling positive and negative symptoms and their treatment

2003

View full text Add to dashboard Cite

show abstract

“…In particular, at least some of these projections have an inhibitory role, as it has been reported that the administration of DOI, a partial agonist of HTR2A/2C with hallucinogenic properties, is associated with a reduce firing of serotonin neurons, in the ventral part of the raphe nuclei mainly, and a enhanced tone of dopaminergic system [Aghajanian et al, 1970;Garratt et al, 1991;Kidd et al, 1991]. The inhibiting action of the serotonin system is not probably under the direct control of serotonin neurons, since dopaminergic neurons do not express HTR2C mRNA.…”

Section: Htr2c Agonist-antagonist Challengesmentioning

confidence: 98%

Focus on HTR2C: A possible suggestion for genetic studies of complex disorders

Drago

Serretti

2009

American J of Med Genetics Pt B

View full text Add to dashboard Cite

HTR2C is one of the most relevant and investigated serotonin receptors. Its role in important brain structures such as the midbrain, the lateral septal complex, the hypothalamus, the olfactory bulb, the pons, the choroid plexus, the nucleus pallidus, the striatum and the amygdala, the nucleus accumbens and the anterior cingulated gyrus candidate it as a promising target for genetic association studies. The biological relevance of these brain structures is reviewed by way of the focus on HTR2C activity, with a special attention paid to psychiatric disorders. Evidence from the genetic association studies that dealt with HTR2C is reviewed and discussed alongside the findings derived from the neuronatmic investigations. The reasons for the discrepancies between these two sets of reports are discussed. As a result, HTR2C is shown to play a pivotal role in many different psychiatric behaviors or psychiatric related disrupted molecular balances, nevertheless, genetic association studies brought inconsistent results so far. The most replicated association involve the feeding behavior and antipsychotic induced side effects, both weight gain and motor related: Cys23Ser (rs6318) and -759C/T (rs3813929) report the most consistent results. The lack of association found in other independent studies dampens the clinical impact of these reports. Here, we report a possible explanation for discrepant findings that is poorly or not at all usually considered, that is that HTR2C may exert different or even opposite activities in the brain depending on the structure analyzed and that mRNA editing activity may compensate possible genetically controlled functional effects. The incomplete coverage of the HTR2C variants is proposed as the best cost-benefit ratio bias to fix. The evidence of brain area specific HTR2C mRNA editing opens a debate about how the brain can differently modulate stress events, and process antidepressant treatments, in different brain areas. The mRNA editing activity on HTR2C may play a major role for the negative association results.

show abstract

“…The resulting activation of phospholipase C (PLC) increases hydrolysis of inositol phosphates and elevates cytosolic Ca 2+ [18], [19]. 5-HT 2 Rs are located post-synaptically [20]–[22], and there is evidence that they modulate neurotransmission at various central and peripheral synaptic sites [23], [24].…”

Section: Introductionmentioning

confidence: 99%

Expression and Function of Serotonin 2A and 2B Receptors in the Mammalian Respiratory Network

et al. 2011

View full text Add to dashboard Cite

Neurons of the respiratory network in the lower brainstem express a variety of serotonin receptors (5-HTRs) that act primarily through adenylyl cyclase. However, there is one receptor family including 5-HT2A, 5-HT2B, and 5-HT2C receptors that are directed towards protein kinase C (PKC). In contrast to 5-HT2ARs, expression and function of 5-HT2BRs within the respiratory network are still unclear. 5-HT2BR utilizes a Gq-mediated signaling cascade involving calcium and leading to activation of phospholipase C and IP3/DAG pathways. Based on previous studies, this signal pathway appears to mediate excitatory actions on respiration. In the present study, we analyzed receptor expression in pontine and medullary regions of the respiratory network both at the transcriptional and translational level using quantitative RT-PCR and self-made as well as commercially available antibodies, respectively. In addition we measured effects of selective agonists and antagonists for 5-HT2ARs and 5-HT2BRs given intra-arterially on phrenic nerve discharges in juvenile rats using the perfused brainstem preparation. The drugs caused significant changes in discharge activity. Co-administration of both agonists revealed a dominance of the 5-HT2BR. Given the nature of the signaling pathways, we investigated whether intracellular calcium may explain effects observed in the respiratory network. Taken together, the results of this study suggest a significant role of both receptors in respiratory network modulation.

show abstract

Inhibition of 5-hydroxytryptamine neuronal activity by the 5-HT agonist, DOI

Cited by 60 publications

References 15 publications

The "two-headed" latent inhibition model of schizophrenia: modeling positive and negative symptoms and their treatment

The "two-headed" latent inhibition model of schizophrenia: modeling positive and negative symptoms and their treatment

Focus on HTR2C: A possible suggestion for genetic studies of complex disorders

Expression and Function of Serotonin 2A and 2B Receptors in the Mammalian Respiratory Network

Contact Info

Product

Resources

About