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Modulation of GABA release from the thalamic reticular nucleus by cocaine and caffeine: role of serotonin receptors
Author(s) -
Goitia Belén,
RiveroEcheto María Celeste,
Weisstaub Noelia V.,
Gingrich Jay A.,
GarciaRill Edgar,
Bisagno Verónica,
Urbano Francisco J.
Publication year - 2016
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.13398
Subject(s) - serotonin , serotonergic , thalamic reticular nucleus , chemistry , 5 ht receptor , neurotransmission , neuroscience , inhibitory postsynaptic potential , receptor , gabaa receptor , neurotransmitter , medicine , endocrinology , pharmacology , biology , biochemistry
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 GABA ergic transmission from thalamic reticular nucleus. We combined whole‐cell patch clamp recordings of miniature inhibitory post‐synaptic currents (m IPSC s) in ventrobasal thalamic neurons during local ( puff ) application of 5‐ HT in wild type ( WT ) or knockout mice lacking 5‐ HT 2A receptors (5‐ HT 2A −/−). Inhibition of m IPSC s frequency by low (10 μM) and high (100 μM) 5‐ HT concentrations was observed in ventrobasal neurons from 5‐ HT 2A −/− mice. In WT mice, only 100 μM 5‐ HT significantly reduced m IPSC s frequency. In 5‐ HT 2A −/− mice, NAN ‐190, a specific 5‐ HT 1A antagonist, prevented the 100 μM 5‐ HT inhibition while blocking H‐currents that prolonged inhibition during post‐puff periods. The inhibitory effects of 100 μM 5‐ HT were enhanced in cocaine binge‐treated 5‐ HT 2A −/− mice. Caffeine binge treatment did not affect 5‐ HT ‐mediated inhibition. Our findings suggest that both 5‐ HT 1A and 5‐ HT 2A 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.Our findings suggest that both 5‐HT 1A , 5‐HT 2A and A1 receptors are present in pre‐synaptic TRN terminals. 5‐HT 1A and A1 receptors would down‐regulate adenylate cyclase, whereas 5‐HT 1A would also increase the probability of the opening of G‐protein‐activated inwardly rectifying K + channels (GIRK). Sustained opening of GIRK channels would hyperpolarize pre‐synaptic terminals activating H‐currents, resulting in less GABA release. 5‐HT 2A ‐would activate PLC and IP 3 , increasing intracellular [Ca 2+ ] and thus facilitating GABA release.