Role of 5-HT1A and 5-HT2A in cocaine-mediated modulation of GABA release from the thalamic reticular nucleus

GOITIA BELEN; NOELIA V WEISSTAUB; JAY A GINGRICH; FRANCISCO URBANO

Washington

Congreso; Annual Meeting for the Society for Neuroscience; 2014

Society for Neuroscience

The thalamic reticular nucleus (TRN) is a thin layer of GABAergic neurons that project to sensory thalamicnuclei and are interconnected by GABAergic terminals and gap junctions. In rodents, the lack ofGABAergic interneurons in the thalamic ventrobasal (VB) nucleus is compensated by GABAergic TRN afferents.TRN neurons have intrinsic properties that allow them to generate action potentials and membranepotential oscillations at a wide range of frequencies modulated by monoamines and GABA.Cocaine is known to inhibit monoamine transporters (DAT, SERT and NET), elevating synaptic levels ofdopamine, norepinephrine and serotonin. Methykphenidate (MPH), a drug widely used to treat childrendiagnosed with ADHD, mainly inhibits DAT and NET, but not SERT.In previous work we observed several dierences regarding thalamic GABAergic transmission in micetreated with either a cocaine binge (3 i.p. injections, 15mg/kg each, 1 hour apart) or a MPH binge: cocaineinduced a greater spontaneous GABA minis frequency compared to MPH, and only cocaine inducedfacilitation of GABA release (measured by paired-pulse ratio) from the TRN to the VB nucleus,suggesting that the eects of cocaine are mediated by changes in serotonergic transmission.