Cross-Modulation Between GABAB and 5-HT Receptors: A Link Between Anxiety and Depression?
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.
KeywordsPyramidal Neuron GABAB Receptor Synaptic Potential Paired Pulse Facilitation Heterologous Desensitization
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