Journal
JOURNAL OF NEUROCHEMISTRY
Volume 136, Issue 3, Pages 526-535Publisher
WILEY
DOI: 10.1111/jnc.13398
Keywords
caffeine; cocaine; GABA; serotonin; thalamic reticular nucleus
Categories
Funding
- FONCYT-Agencia Nacional de Promocion Cientifica y Tecnologica [BID 1728 OC.AR., PICT-2012-1769, UBACYT 2014-2017, 20120130101305BA]
- FONCYT-Agencia Nacional de Promocion Cientifica y Tecnologica Argentina [BID 1728 OC.AR., PICT 2012-0924]
- NIH [R01 NS020246]
- core facilities of the Center for Translational Neuroscience - NIH [P20 GM103425, P30 GM110702]
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Serotonin receptors are targets of drug therapies for a variety of neuropsychiatric and neurodegenerative disorders. Cocaine inhibits the re-uptake of serotonin (5-HT), dopamine, and noradrenaline, whereas caffeine blocks adenosine receptors and opens ryanodine receptors in the endoplasmic reticulum. We studied how 5-HT and adenosine affected spontaneous GABAergic transmission from thalamic reticular nucleus. We combined whole-cell patch clamp recordings of miniature inhibitory post-synaptic currents (mIPSCs) in ventrobasal thalamic neurons during local (puff) application of 5-HT in wild type (WT) or knockout mice lacking 5-HT2A receptors (5-HT2A-/-). Inhibition of mIPSCs frequency by low (10 mu M) and high (100 mu M) 5-HT concentrations was observed in ventrobasal neurons from 5-HT2A-/- mice. In WT mice, only 100 mu M 5-HT significantly reduced mIPSCs frequency. In 5HT(2A)-/- mice, NAN-190, a specific 5-HT1A antagonist, prevented the 100 mu M 5-HT inhibition while blocking H-currents that prolonged inhibition during post-puff periods. The inhibitory effects of 100 mu M 5-HT were enhanced in cocaine binge-treated 5-HT2A-/- mice. Caffeine binge treatment did not affect 5-HT-mediated inhibition. Our findings suggest that both 5-HT1A and 5-HT2A receptors are present in pre-synaptic thalamic reticular nucleus terminals. Serotonergic-mediated inhibition of GABA release could underlie aberrant thalamocortical physiology described after repetitive consumption of cocaine.
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