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

GOITIA B; WEISSTAUB N; GINGRICH J; GARCIA-RILL E; BISAGNO V; URBANO FJ

Washington, DC

Congreso; 2014 SOCIETY FOR NEUROSCIENCE MEETING, Washington D.C., Nov. 15-19.; 2014

Society for Neuroscience

Methylphenidate (MPH), a drug widely used to treat children diagnosed with ADHD, and cocaine (Coc) inhibit the re-uptake of dopamine and norepinephrine. Cocaine, unlike MPH, also inhibits the re-uptake of serotonin (5-HT). Previously, we observed that the frequency of spontaneous GABA release from thalamic reticular nucleus (Ret) neurons is increased in slices from mice treated with a Coc binge (3 i.p. injections, 15mg/kg each, 1 hour apart) but not in those from animals treated with an MPH binge, suggesting that the effect of Coc is mediated by changes in serotonergic transmission. Thus, we investigated the effect of 5-HT receptors agonists and antagonists in control and Coc treated thalamocortical slices from mice using patch clamp. Additionally, we administered Coc to mice lacking 5-HT2A receptors. We first recorded miniature inhibitory post-synaptic potentials (mIPSPs) from ventrobasal neurons using thalamocortical slices from control mice in the presence of 5-HT and 5-HT1A or 5HT2A/2C agonists ((±)-8-OH-DPAT, (±)-DOI hydrochloride; both 10μM) and antagonists (NAN-190 hydrobromide, ketanserin; both 25μM). Our results show that the effect of bath-applied 5-HT (100 μM, >15min) on mIPSP frequency resembles that of Coc (5-HT, Coc vs. control, Kruskal Wallis test, p