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Localization and function of monoamine receptors in prefrontal cortex: Therapeutic implications

Francesc Artigas1*, Pau Celada1, Noemí Santana1 and Guadalupe Mengod1
  • 1 IIBB-CSIC (IDIBAPS),CIBERSAM and CIBERNED, Department of Neurochemistry and Neuropharmacology, Spain

The prefrontal cortex (PFC) plays a key role in cognitive processes, such as working (short-term) memory and executive functions as well as in action planning, decision taking and the processing of emotional signals. An abnormal PFC function has been reported in severe neuropsychiatric diseases such as major depression and schizophrenia. The PFC represents the highest level of integration of all cortical areas.
Pyramidal neurons of the PFC receive afferents from many cortical and subcortical areas. Once processed, information is sent back to the rest of the brain, on which the PFC exerts a top-down control. In addition to glutamate and GABA, the PFC contains a large population of monoamine (dopamine, DA; noradrenaline, NA; and serotonin, 5-HT) receptors whose activation by the endogenous neurotransmitter or exogenous drugs modulates PFC function. In recent years, we examined the expression of several 5-HT (5-HT1A, 5-HT2A, 5-HT3), DA (D1, D2) and NA receptors (α1-adrenergic) in pyramidal and GABAergic neurons of the rat PFC using double in situ hybridization histochemistry (1-4). Some of these receptors are expressed by a large proportion (up to 80%) of pyramidal neurons and are highly co-localized (5-HT1A and 5-HT2A, α1-adrenergic and 5-HT2A). In contrast, the proportion of GABAergic interneurons expressing monoamine receptors is much lower (typically 20-40%) with the exception of α1-adrenergic receptors, which can be expressed by most interneurons.
Numerous studies have focused on the physiological role of the atecholamines in controlling the activity of PFC neurons. The role of 5-HT has been much less studied despite second generation (atypical) antipsychotics used in the treatment of schizophrenia have high affinity for some 5-HT receptors and drugs acting on these receptors (e.g., LSD, DOI, etc.) have hallucinogenic properties. The physiological release of 5-HT, produced by stimulation of the dorsal or median raphe nuclei, evokes inhibitions (5-HT1A receptor-mediated) and excitations (5-HT2A receptor-mediated) in PFC pyramidal neurons (5). The administration of DOI, a preferential 5-HT2A receptor agonist, produced an overall increase of pyramidal discharge (6) and reduced low frequency oscillations in PFC (7). These effects are entirely similar to those produced by phencyclidine (PCP), a non-competitive NMDA receptor antagonist used as a pharmacological model of schizophrenia (8). Interestingly, both the actions of DOI and PCP are reversed by classical and atypical antipsychotics (7, 8), suggesting a direct link with the pathophysiology of schizophrenia. Whereas the action of atypical antipsychotics can be mediated by a local action on PFC 5-HT2A receptors, the action of classical antipsychotics (DA D2 blockers) may also involve distal actions on ventral striatum, which may later affect PFC via thalamic inputs.

References

1. Santana N, Bortolozzi A, Serrats J, Mengod G, Artigas F (2004) Cereb Cortex 14:1100-1109

2. Amargós-Bosch M, Bortolozzi A, Puig MV, Serrats J, Adell A, Celada P, Toth M, Mengod G, Artigas F (2004) Cereb Cortex 14: 281-299.

3. Puig MV, Santana N, Celada P, Mengod G, Artigas F (2004) Cereb Cortex 14: 1365-1375

4. Santana N, Mengod G, Artigas F (2008) Cereb Cortex. Aug 9. PMID: 18689859

5. Puig MV, Artigas F, Celada P (2005) Cereb Cortex 15:1-14

6. Puig MV, Celada P, Díaz-Mataix L, Artigas F (2003) Cereb Cortex 13: 870-882

7. Celada P, Puig MV, Díaz-Mataix L, Artigas F (2008) Biol Psychiatry 64:392-400

8. Kargieman L, Santana N, Mengod G, Celada P, Artigas F (2007) Proc Natl Acad Sci USA 104:14843-14848

Conference: 3rd Mediterranean Conference of Neuroscience , Alexandria, Egypt, 13 Dec - 16 Dec, 2009.

Presentation Type: Oral Presentation

Topic: Plenary lectures

Citation: Artigas F, Celada P, Santana N and Mengod G (2009). Localization and function of monoamine receptors in prefrontal cortex: Therapeutic implications. Front. Neurosci. Conference Abstract: 3rd Mediterranean Conference of Neuroscience . doi: 10.3389/conf.neuro.01.2009.16.018

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Received: 18 Nov 2009; Published Online: 18 Nov 2009.

* Correspondence: Francesc Artigas, IIBB-CSIC (IDIBAPS),CIBERSAM and CIBERNED, Department of Neurochemistry and Neuropharmacology, 08036 Barcelona, Spain, fapnqi@iibb.csic.es