Open AccessNeuroanatomical Relationships between Orexin/Hypocretin-Containing Neurons/Nerve Fibers and Nicotine-Induced c-Fos-Activated Cells of the Reward-Addiction Neurocircuitry
Author(s) -
Ozra Dehkordi,
Jed E. Rose,
Martha I. Dávila-Garcı́a,
Richard M. Millis,
Samar Ali Mirzaei,
Kebreten F. Manaye,
Annapurni JayamTrouth
Publication year - 2017
Publication title -
journal of alcohol drug dependence
Language(s) - English
Resource type - Journals
ISSN - 2329-6488
DOI - 10.4172/2329-6488.1000273
Subject(s) - orexin , ventral tegmental area , neuroscience , nucleus accumbens , locus coeruleus , nicotine , lateral hypothalamus , hypothalamus , dorsal raphe nucleus , orexin a , tyrosine hydroxylase , dopaminergic , chemistry , medicine , dopamine , endocrinology , nucleus , biology , neuropeptide , serotonin , serotonergic , receptor
Orexin/hypocretin-containing neurons in lateral hypothalamus (LH) are implicated in the neurobiology of nicotine addiction. However, the neuroanatomical relationships between orexin-neurons/nerve fibers and nicotine-activated cells within the reward-addiction neurocircuitry is not known. In the present study in mice, we first used c-Fos immunohistochemistry to identify CNS cells stimulated by an acute single injection of nicotine (NIC, 2 mg/kg, IP). Sequential double-labelling was then performed to identify the location of orexin-containing neurons and nerve fibers with respect to NIC-induced c-Fos activated cells and/or tyrosine hydroxylase (TH) immunoreactive (IR) cells of the mesocorticolimbic reward-addiction pathways. Orexin-IR nerve fibers and terminals were detected at multiple sites of the NIC reward-addiction circuitry in close apposition to, and intermingled with, NIC-induced c-Fos-IR cells of locus coeruleus (LC), ventral tegmental area (VTA), nucleus accumbens (Acb), LH and paraventricular thalamic nucleus (PVT). Double-labelling of orexin with TH showed frequent contact between orexin-IR nerve fibers and noradrenergic cells of LC. However, there was infrequent contact between the orexinergic fibers and the TH-expressing dopaminergic cells of VTA, dorsal raphe nucleus (DR), posterior hypothalamus (DA11), arcuate hypothalamic nucleus (DA12) and periventricular areas (DA14). The close anatomical contact between orexinergic nerve fibers and NIC-activated cells at multiple sites of the reward-addiction pathways suggests that orexinergic projections from LH are likely to be involved in modulating activity of the neurons that are directly impacted by acute administration of nicotine.