Pyramidal neurons in the sensory-motor cortex express multiple types of metabotropic receptors. Simultaneous application of serotonin (5-HT) and GABAB agonists produces a reduction of the neurotransmitter release probability throughout the activation of the GABAB and 5-HT1A receptors. Since some of these receptors may be coexpressed in a set of neurons, we examined the consequence of the simultaneous activation of GABAB and 5-HT receptors and investigated their influence on neurotransmitter release probability in the sensorimotor cortex of the rat using extracellular stimulation with a paired pulse protocol. We found that the effect of 5-HT is occluded when the GABAB receptor is previously activated with baclofen. The effect is mimicked by the 5-HT agonist DOI and prevented by the 5-HT2 antagonist ritanserin. Since prefrontal cortical 5-HT terminals may contact “en passant” fibers and release the 5-HT by volume transmission, and because 5-HT1A and 5-HT2A/C receptors are coexpressed in pyramidal neurons, they may reciprocally modify each other’s metabolic pathways, leading to the production of nonlinear interactions in this cortical area. The potential implications of the cross-talk between 5-HT and GABAB receptors are discussed in terms of the consequence of the use of selective serotonin reuptake inhibitors in the treatment of the depression.
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6.6 References
Amargós-Bosch, M., Bortolozzi, A., Puig, M. V., Serrats, J., Adell, A., Celada, P., Toth, M., Mengod, G. and Artigas, F. (2004) Co-expression and in vivo interaction of serotonin1A and serotonin2A receptors in pyramidal neurons of prefrontal cortex. Cereb Cortex. 14, 281-299.
Barnes, N. M. and Sharp, T. (1999) A review of central 5-HT receptors and their function. Neu-ropharmacology 38, 1083-1152.
Carrasco, G. A., Van de Kar, L. D., Jia, C., Xu, H., Chen, Z., Chadda, R., Garcia, F., Muma, N. A. and Battaglia, G. (2007) Single exposure to a serotonin 1A receptor agonist, (+)8-hydroxy-2-(di-n-propylamino)-tetralin, produces a prolonged heterologous desensitization of serotonin 2A receptors in neuroendocrine neurons in vivo. J Pharmacol Exp Ther. 320, 1078-1086.
Celada, P., Puig, M., Amargos-Bosch, M., Adell, A. and Artigas, F. (2004) The therapeutic role of 5-HT1A and 5-HT2A receptors in depression. J Psychiatry Neurosci. 29, 252-265.
Colino, A., Munoz, J. and Vara, H. (2002) [Short term synaptic plasticity]. Rev Neurol. 34, 593-599.
Cordeaux, Y. and Hill, S. J. (2002) Mechanisms of cross-talk between G-protein-coupled recep-tors. Neurosignals. 11, 45-57.
Evans, K. L., Cropper, J. D., Berg, K. A. and Clarke, W. P. (2001) Mechanisms of regulation of agonist efficacy at the 5-HT1A receptor by phospholipid-derived signaling components. J Pharmacol Exp Ther. 297, 1025-1035.
Foehring, R. C., van Brederode, J. F., Kinney, G. A. and Spain, W. J. (2002) Serotonergic modu-lation of supragranular neurons in rat sensorimotor cortex. J Neurosci. 22, 8238-8250.
Hempel, C. M., Hartman, K. H., Wang, X. J., Turrigiano, G. G. and Nelson, S. B. (2000) Multi-ple forms of short-term plasticity at excitatory synapses in rat medial prefrontal cortex. J Neurophysiol. 83, 3031-3041.
Hirschfeld, R. M. (2001) The comorbidity of major depression and anxiety disorders: Rec-ognition and management in primary care. Prim Care Companion J Clin Psychiatry. 3, 244-254.
Marek, G. J., Carpenter, L. L., McDougle, C. J. and Price, L. H. (2003) Synergistic action of 5-HT2A antagonists and selective serotonin reuptake inhibitors in neuropsychiatric disorders. Neuropsychopharmacology. 28, 402-412.
Mombereau, C., Kaupmann, K., Gassmann, M., Bettler, B., van der Putten, H. and Cryan, J. F. (2005) Altered anxiety and depression-related behaviour in mice lacking GABAB(2) re-ceptor subunits. Neuroreport. 16, 307-310.
Murakoshi, T., Song, S. Y., Konishi, S. and Tanabe, T. (2001) Multiple G-protein-coupled recep-tors mediate presynaptic inhibition at single excitatory synapses in the rat visual cortex. Neurosci Lett. 309, 117-120.
Nakagawa, Y., Ishima, T., Ishibashi, Y., Yoshii, T. and Takashima, T. (1996) Involvement of GABABreceptor systems in action of antidepressants: baclofen but not bicuculline attenuates the effects of antidepressants on the forced swim test in rats. Brain Res. 709, 215-220.
Pilc, A. and Nowak, G. (2005) GABAergic hypotheses of anxiety and depression: focus on GABA-B receptors. Drugs Today (Barc). 41, 755-766.
Ridet, I. and Privat, A. (2000) Volume transmission. Trends Neurosci. 23, 58-59.
Slattery, D. A., Desrayaud, S. and Cryan, J. F. (2005) GABAB receptor antagonist-mediated antidepressant-like behavior is serotonin-dependent. J Pharmacol Exp Ther. 312, 290-296.
Sokal, D. M., Giarola, A. S. and Large, C. H. (2005) Effects of GABAB , 5-HT 1A, and 5-HT2 receptor stimulation on activation and inhibition of the rat lateral amygdala following medial geniculate nucleus stimulation in vivo. Brain Res. 1031, 141-150.
Taniyama, K., Takeda, K., Ando, H., Kuno, T. and Tanaka, C. (1991) Expression of the GABAB receptor in Xenopus oocytes and inhibition of the response by activation of protein kinase C. FEBS Lett. 278, 222-224.
Thomson, A. M. (2000) Facilitation, augmentation and potentiation at central synapses. Trends Neurosci. 23, 305-312.
Torres-Escalante, J. L., Barral, J. A., Ibarra-Villa, M. D., Perez-Burgos, A., Gongora-Alfaro, J. L. and Pineda, J. C. (2004) 5-HT1A,5-HT2, and GABAB receptors interact to modulate neurotransmitter release probability in layer 2/3 somatosensory rat cortex as evaluated by the paired pulse protocol. J Neurosci Res. 78, 268-278.
Tournois, C., Mutel, V., Manivet, P., Launay, J. M. and Kellermann, O. (1998) Cross-talk be-tween 5-hydroxytryptamine receptors in a serotonergic cell line. Involvement of arachidonic acid metabolism. J Biol Chem. 273, 17498-17503.
Wang, S. J., Coutinho, V. and Sihra, T. S. (2002) Presynaptic cross-talk of beta-adrenoreceptor and 5-hydroxytryptamine receptor signalling in the modulation of glutamate release from cerebrocortical nerve terminals. Br J Pharmacol. 137, 1371-1379.
Wang, S. J., Cheng, L. L. and Gean, P. W. (1999) Cross-modulation of synaptic plasticity by beta-adrenergic and 5-HT1A receptors in the rat basolateral amygdala. J Neurosci. 19, 570-577.
Xiang, Z., Wang, L. and Kitai, S. T. (2005) Modulation of spontaneous firing in rat subthalamic neurons by 5-HT receptor subtypes. J Neurophysiol. 93, 1145-1157.
Zhang, Y., D’Souza, D., Raap, D. K., Garcia, F., Battaglia, G., Muma, N. A. and Van de Kar, L. D. (2001) Characterization of the functional heterologous desensitization of hypothalamic 5-HT1A receptors after 5-HT2A receptor activation. J Neurosci. 21, 7919-7927.
Zhang, Y., Gray, T. S., D’Souza, D. N., Carrasco, G. A., Damjanoska, K. J., Dudas, B., Garcia, F., Zainelli, G. M., Sullivan Hanley, N. R., Battaglia, G., Muma, N. A. and Van de Kar, L. D. (2004) Desensitization of 5-HT1A receptors by 5-HT2A receptors in neuroendocrine neurons in vivo. J Pharmacol Exp Ther. 310, 59-66.
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Pineda, J.C., Góngora-Alfaro, J.L. (2007). Cross-Modulation Between GABAB and 5-HT Receptors: A Link Between Anxiety and Depression?. In: Tseng, KY., Atzori, M. (eds) Monoaminergic Modulation of Cortical Excitability. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-72256-6_6
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