%0 Journal Article
%T Dorsal raphe serotonin neurons inhibit operant responding for reward via inputs to the ventral tegmental area but not the nucleus accumbens: evidence from studies combining optogenetic stimulation and serotonin reuptake inhibition
%A Andrew R. Abela
%A Caleb J. Browne
%A Duong Chu
%A Evelyn K. Lambe
%A Paul J. Fletcher
%A Xiaodong Ji
%A Zhaoxia Li
%J Archive of "Neuropsychopharmacology".
%D 2019
%R 10.1038/s41386-018-0271-x
%X Optogenetic stimulation causes dorsal raphe nucleus (DRN) 5-HT neuron activation and enhances downstream 5-HT release, but does not alter operant responding for reward. a Expression of ChR2-EYFP specifically in 5-HT neurons was achieved by crossing Ai32+/+ mice and ePet-cre+/£¿ mice. b Representative coronal section showing ChR2-EYFP expression in the DRN: left, 5-HT neurons immunostained for tryptophan hydroxylase-2, a marker of 5-HT neurons; middle, cells expressing ChR2-EYFP; right, merge of tryptophan hydroxylase-2 and ChR2-EYFP channels. Scale bar represents 100£¿¦Ìm. c Schematic for ex vivo patch-clamp recordings of ChR2-EYFP expressing DRN neurons. d Characteristic electrophysiological response of an EYFP-positive serotonergic DRN neuron to current steps and 2£¿Hz photostimulation trains. e Top: average (¡ÀSEM) firing frequencies of DRN 5-HT neurons (n£¿=£¿13) elicited by 30£¿s trains of optogenetic stimulation (2¨C10£¿Hz). Bottom: Averaged trace illustrating that extended photostimulation (2£¿Hz, 200£¿s) can maintain a significantly elevated firing frequency compared to baseline (paired-samples t-test: t(7)£¿=£¿5.52, p£¿<£¿0.001), when tested in a subset of DRN 5-HT neurons. f Schematic for in vivo microdialysis with optogenetic stimulation of ChR2-EYFP expressing DRN 5-HT neurons. g Average (¡ÀSEM) extracellular 5-HT concentration within the NAc from anesthetized ChR2+ mice (n£¿=£¿5) during periods of photostimulation (blue shaded areas) or no photostimulation (unshaded areas). *p£¿<£¿0.05 vs. previous baseline sample from post hoc analysis. h Schematic for optogenetic stimulation (473£¿nm light, 10£¿mW, 10£¿ms pulses) of DRN 5-HT neurons throughout tests of operant responding for saccharin. i Optogenetic stimulation of DRN 5-HT neurons does not alter operant responding for saccharin: mean lever presses (¡ÀSEM) for saccharin was not different between ChR2£¿ (n£¿=£¿10; white bars) and ChR2+ mice (n£¿=£¿11; green bars) at any photostimulation frequency tested (Group£¿¡Á£¿Frequency: F(3,57)£¿=£¿0.06, ns; Group: F(3,57)£¿=£¿2.94, ns; independent-samples t-tests: all t(19)£¿<£¿1.57, all p£¿>£¿0.066
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6372654/