https://ogma.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 Chemogenetic activation of the lateral hypothalamus reverses early life stress-induced deficits in motivational drive https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:32927 Tue 14 Aug 2018 14:59:36 AEST ]]> Activation of lateral hypothalamic group III metabotropic glutamate receptors suppresses cocaine-seeking following abstinence and normalizes drug-associated increases in excitatory drive to orexin/hypocretin cells https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:35731 in-vivo, including in animals with cocaine experience. First, we verified that group III mGluRs regulate orexin cell activity in behaving animals by showing that intra-LHA infusions of the selective agonist L-(+)-2-Amino-4-phosphonobutyric acid (L-AP4) reduces c-fos expression in orexin cells following 24 h food deprivation. Next, we extended these findings to show that intra-LHA L-AP4 infusions reduced discriminative stimulus-driven cocaine-seeking following withdrawal. Importantly, L-AP4 had no effect on lever pressing for sucrose pellets or general motoric behavior. Finally, using whole-cell patch-clamp recordings from identified orexin cells in orexin-GFP transgenic mice, we show enhanced presynaptic drive to orexin cells following 14d withdrawal and that this plasticity can be normalized by L-AP4. Together, these data indicate that activation of group III mGluRs in LHA reduces orexin cell activity in vivo and may be an effective strategy to suppress cocaine-seeking behavior following withdrawal. These effects are likely mediated, at least in part, by normalization of presynaptic plasticity at orexin cells that occurs as a result of cocaine exposure. This article is part of the Special Issue entitled ‘Hypothalamic Control of Homeostasis’.]]> Thu 28 Oct 2021 13:02:35 AEDT ]]>