Expression of Serotonin1A and Serotonin2A Receptors in Pyramidal and GABAergic Neurons of the Rat Prefrontal Cortex

Santana, Noemí

doi:10.1093/cercor/bhh070

Cited by 440 publications

(399 citation statements)

References 77 publications

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“…Interneurons in the mPFC can be targets of 5-HT action because they are known to express 5-HT1A, 5-HT2A, and 5-HT3 receptors (Morales et al, 1996;Puig et al, 2004;Santana et al, 2004). Our present results indicate that 94% of PSA-NCAM expressing neurons in the mPFC express the 5-HT-3 receptor and that they lack 5-HT1A and 5-HT2A receptors, suggesting that 5-HT actions on PSA-NCAM expression occur through 5-HT3 receptors.…”

Section: Involvement Of 5-ht In the Modulation Of Psa-ncam Expressionmentioning

confidence: 49%

“…This result is in accordance with previous reports that indicate an extra-synaptic action of 5-HT, because this neurotransmitter is able to diffuse considerable distances from its point of release (De Miguel and Trueta, 2005) and consequently, once secreted, 5-HT can act on wide areas of the CNS. In fact, 5-HT receptors can be found widely distributed in the mPFC (Morales et al, 1996;Puig et al, 2004;Santana et al, 2004) and we detect increases in PSA-NCAM expression, specially in the neuropil, in every layer of the mPFC subdivisions. Thus, although the density of 5-HT fibers in superficial layers of the mPFC is higher, the increases in PSA-NCAM expression detected in deeper layers may also be explained by 5-HT action.…”

Section: Involvement Of 5-ht In the Modulation Of Psa-ncam Expressionmentioning

confidence: 65%

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Chronic Fluoxetine Treatment Increases the Expression of PSA-NCAM in the Medial Prefrontal Cortex

Varea

Blasco-Ibáñez

Gómez-Climent

et al. 2006

Neuropsychopharmacol

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Recent hypotheses suggest that changes in neuronal structure and connectivity may underlie the etiology of depression. The medial prefrontal cortex (mPFC) is affected by depression and shows neuronal remodeling during adulthood. This plasticity may be mediated by the polysialylated form of the neural cell adhesion molecule (PSA-NCAM), which is intensely expressed in the adult mPFC. As the expression of PSA-NCAM is increased by serotonin in other cerebral regions, antidepressants acting on serotonin reuptake may influence PSA-NCAM expression and thus counteract the effects of depression by modulating neuronal structural plasticity. Using immunohistochemistry, we have studied the relationship between serotoninergic fibers and PSA-NCAM expressing neurons in the adult rat mPFC and the expression of serotonin receptors in these cells. The effects of fluoxetine treatment for 14 days on mPFC PSA-NCAM expression have also been analyzed. Although serotoninergic fibers usually do not contact PSA-NCAM immunoreactive neurons, most of these cells express 5-HT3 receptors. In general, chronic fluoxetine treatment induces significant increases in the number of PSA-NCAM immunoreactive neurons and in neuropil immunostaining and coadministration of the 5-HT3 antagonist ondansetron blocks the effects of fluoxetine on PSA-NCAM expression. These results indicate that fluoxetine, acting through 5-HT3 receptors, can modulate PSA-NCAM expression in the mPFC. This modulation may mediate the structural plasticity of this cortical region and opens new perspectives on the study of the molecular bases of depression.

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Section: Involvement Of 5-ht In the Modulation Of Psa-ncam Expressionmentioning

confidence: 49%

Section: Involvement Of 5-ht In the Modulation Of Psa-ncam Expressionmentioning

confidence: 65%

Chronic Fluoxetine Treatment Increases the Expression of PSA-NCAM in the Medial Prefrontal Cortex

Varea

Blasco-Ibáñez

Gómez-Climent

et al. 2006

Neuropsychopharmacol

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“…In the hippocampus and cortex, 5-HT1A receptors are found in pyramidal cells. In the PFC, they are co-localized with 5-HT2A receptors (Santana et al, 2004). 5-HT1A mRNA is also observed in cortical GABAergic cells (Santana et al, 2004).…”

Section: -Ht1a Localizationmentioning

confidence: 99%

“…In the PFC, they are co-localized with 5-HT2A receptors (Santana et al, 2004). 5-HT1A mRNA is also observed in cortical GABAergic cells (Santana et al, 2004). However, there is controversy regarding their subcellular localization.…”

Section: -Ht1a Localizationmentioning

confidence: 99%

Pharmacologic mechanisms of serotonergic regulation of dopamine neurotransmission

Alex

Pehek

2007

Pharmacology & Therapeutics

535

311

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The neurotransmitter dopamine (DA) has a long association with normal functions such as motor control, cognition, and reward, as well as a number of syndromes including drug abuse, schizophrenia, and Parkinson's disease. Studies show that serotonin (5-HT) acts through several 5-HT receptors in the brain to modulate DA neurons in all three major dopaminergic pathways. There are at least 14 5-HT receptor subtypes, many of which have been shown to play some role in mediating 5-HT/DA interactions. Several subtypes, including the 5-HT1A, 5-HT1B, 5-HT2A, 5-HT3 and 5-HT4 receptors, act to facilitate DA release, while the 5-HT2C receptor mediates an inhibitory effect of 5-HT on DA release. Most 5-HT receptor subtypes only modulate DA release when 5-HT and/or DA neurons are stimulated, but the 5-HT2C receptor, characterized by high levels of constitutive activity, inhibits tonic as well as evoked DA release. This review summarizes the anatomical evidence for the presence of each 5-HT receptor subtype in dopaminergic regions of the brain and the neuropharmacological evidence demonstrating regulation of each DA pathway. The relevance of 5-HT receptor modulation of DA systems to the development of therapeutics used to treat schizophrenia, depression, and drug abuse is discussed. Lastly, areas are highlighted in which future research would be maximally beneficial to the treatment of these disorders.

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“…These receptors are highly colocalized (80%) in nearly half of the glutamatergic pyramidal neurons of the PFC and they are also present in about 25% of GABA interneurons (Santana et al, 2004). The activation of 5-HT 1A receptors in the PFC inhibits the neuronal output of pyramidal neurons by activation of a hyperpolarizing potassium current; 5-HT 2A facilitates output through a reduction of potassium conductance, reduction of the after-hyperpolarization, and increase in excitatory postsynaptic currents and discharge rate (Aghajanian and Marek, 1997;Andrade and Nicoll, 1987;Araneda and Andrade, 1991;Tanaka and North, 1993).…”

Section: Introductionmentioning

confidence: 99%

Dissociable Contribution of 5-HT1A and 5-HT2A Receptors in the Medial Prefrontal Cortex to Different Aspects of Executive Control such as Impulsivity and Compulsive Perseveration in Rats

Carli

Baviera

Invernizzi

et al. 2005

Neuropsychopharmacol

170

158

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Serotonin (5-HT) receptors are increasingly recognized as major targets for cognitive enhancement in schizophrenia. Several lines of evidence suggest a pathophysiological role for glutamate NMDA receptors in the prefrontal cortex in schizophrenia and associated disorders in attention and executive functioning. We investigated how the interactions between 5-HT 1A and 5-HT 2A and glutamate NMDA receptor mechanisms in the medial prefrontal cortex (mPFC) contribute to the control of different aspects of attentional performance. Rats were trained on a five-choice serial reaction time (5-CSRT) task, which provides indices of attentional functioning (percentage of correct responses), executive control (measured by anticipatory and perseverative responses), and speed. The competitive NMDA receptor antagonist CPP (50 ng/side) was infused directly into the mPFC 5 min after infusion of either 8-OH-DPAT (30 and 100 ng/side) or M100907 (100 and 300 ng/side) into the same brain area. Impairments in attentional functioning induced by CPP were completely abolished by both doses of 8-OH-DPAT or M100907. In addition, M100907 abolished the CPP-induced anticipatory responding but had no effects on perseverative over-responding, while 8-OH-DPAT reduced the perseverative over-responding but had no effects on anticipatory responding induced by CPP. The selective 5-HT 1A receptor antagonist WAY100635 (30 ng/side) antagonized the effects of 8-OH-DPAT (100 ng/side). 8-OH-DPAT at 30 ng/side reduced the latency of correct responses in controls and CPPinjected rats and lowered the percentage of omissions in CPP-injected rats. The data show that 5-HT 1A and 5-HT 2A receptors in the mPFC exert opposing actions on attentional functioning and demonstrate a dissociable contribution of 5-HT 1A and 5-HT 2A receptors in the mPFC to different aspects of executive control such as impulsivity and compulsive perseveration.

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Expression of Serotonin1A and Serotonin2A Receptors in Pyramidal and GABAergic Neurons of the Rat Prefrontal Cortex

Cited by 440 publications

References 77 publications

Chronic Fluoxetine Treatment Increases the Expression of PSA-NCAM in the Medial Prefrontal Cortex

Chronic Fluoxetine Treatment Increases the Expression of PSA-NCAM in the Medial Prefrontal Cortex

Pharmacologic mechanisms of serotonergic regulation of dopamine neurotransmission

Dissociable Contribution of 5-HT1A and 5-HT2A Receptors in the Medial Prefrontal Cortex to Different Aspects of Executive Control such as Impulsivity and Compulsive Perseveration in Rats

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