Dataset Information

Impact of serotonin (5-HT)2C receptors on executive control processes.

ABSTRACT: Although the serotonin (5-hydroxytryptamine, 5-HT) neurotransmitter system has been implicated in modulating executive control processes such as attention, response inhibition, and behavioral flexibility, the contributions of particular serotonin receptors remain unclear. Here, using operant-based behavioral paradigms, we demonstrate that mice with genetically ablated 5-HT2C receptors (2CKO mice) display deficits in executive functions. 2CKO mice were impaired in the acquisition of a visuospatial attention task as assessed in the 5-choice serial reaction time task (5-CSRTT). In this task, 2CKO mice exhibited marked impairment of attentional processes, with normal response inhibition. We assessed dynamic changes in neurotransmitter levels within the nucleus accumbens (NAc) by in vivo microdialysis in task-performing animals. Extracellular dopamine concentrations were elevated in the NAc of 2CKO mice during task performance, indicating that 5-HT2C receptors impact dopamine homeostasis during a visuospatial attention task. These findings raise the possibility that disinhibition of mesolimbic dopamine pathways contributes to impaired attention and perturbed task performance in 2CKO mice. Additionally, in a spatial reversal learning task, 2CKO mice failed to improve their performance over a series of reversals, indicating that intact 5-HT2C receptor signaling is required to accurately respond to repeated changes in reward contingencies. In contrast to the 2CKO phenotype in the 5-CSRTT, wild-type mice treated with the 5-HT2C receptor antagonist SB242084 exhibited diminished response inhibition, suggesting differing effects of acute pharmacological blockade and constitutive loss of 5-HT2C receptor activity. Altogether, these findings provide insights into the serotonergic regulation of executive control processes and suggest that impaired 5-HT2C receptor signaling during development may predispose to executive function disorders.

SUBMITTER: Pennanen L

PROVIDER: S-EPMC3629384 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Impact of serotonin (5-HT)2C receptors on executive control processes.

Pennanen Luis L van der Hart Marieke M Yu Lisa L Tecott Laurence H LH

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 20121213 6

Although the serotonin (5-hydroxytryptamine, 5-HT) neurotransmitter system has been implicated in modulating executive control processes such as attention, response inhibition, and behavioral flexibility, the contributions of particular serotonin receptors remain unclear. Here, using operant-based behavioral paradigms, we demonstrate that mice with genetically ablated 5-HT2C receptors (2CKO mice) display deficits in executive functions. 2CKO mice were impaired in the acquisition of a visuospatia ...[more]

PMID: 23303047

Similar Datasets

Project description:At present the most investigated 5-HT receptor that has been shown to play a role in the control of micturition is the 5-HT(1A) receptor followed by 5-HT(7), 5-HT(2) and 5-HT(3) receptors. Most experiments focus on the control these receptors have on the parasympathetic outflow to the bladder and the somatic outflow to the external urethral sphincter (EUS) in the rat. Furthermore, 5-HT(1A) and 5-HT(7) receptors have been identified as having an excitatory physiological role in the control of bladder function. 5-HT(1A) receptors act, at least in the rat, at both a spinal (probably a heteroreceptor) and supraspinal (probably an autoreceptor) level, while 5-HT(7) receptors only act at a supraspinal level. Additionally, in the rat, 5-HT administered at a spinal or supraspinal site has an excitatory action, although earlier experiments have shown that activating 5-HT-containing brain areas causes inhibition of the bladder. Recent experiments have also indicated that blockade of the 5-HT(1A) receptor pathway shows rapid tolerance. However, no data exist for the development of tolerance for the 5-HT(7) receptor pathway. Neither receptor seems to play a role in the control of the urethra. Regarding 5-HT(2) receptors, activation of this receptor subtype inhibits micturition, and this inhibitory action may occur at a spinal, supraspinal or both levels. Although no physiological role for 5-HT(2C) receptors can yet be identified, 5-HT(2C) receptors have been implicated in the proposed supraspinal tonically active 5-HT(1A) autoreceptor (negative feedback) pathway. This proposition reconciles the data that central 5-HT-containing pathways are inhibitory to micturition, while 5-HT(1A) receptors, although inhibitory to adenylyl cyclase, have an excitatory function. This is because activation of 5-HT(1A) autoreceptors reduces the release of 5-HT thus reducing the activation of the 5-HT(2C) receptors, which are inhibitory in the control of micturition (disinhibition). Furthermore, 5-HT(2A) receptors in the rat and 5-HT(2C) receptors in the guinea pig cause activation of the EUS. In this respect, 5-ht(5A) receptors have also been identified in Onuf's nucleus, the site of somatic motoneurones controlling this sphincter. In the cat there is very little evidence to indicate that 5-HT receptors are involved in micturition except under pathological conditions in which activation of 5-HT(1A) receptors causes inhibition of micturition. Interestingly, under such conditions 5-HT(1A) receptors cause excitation of the EUS. Nevertheless, spinal 5HT(3) receptors have been implicated in the physiological control of micturition in the cat, but not yet in the rat. Overall, the data support the view that 5-HT receptors are important in the control of micturition. However, many more studies are required to fully understand these roles and why there are such species differences.

Dataset Information

Impact of serotonin (5-HT)2C receptors on executive control processes.

Publications

Impact of serotonin (5-HT)2C receptors on executive control processes.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets