title: Nicotine self-administration remodels perineuronal nets in ventral tegmental area and orbitofrontal cortex in adult male rats.
abstract: Nicotine, a major psychoactive component of tobacco smoke, alters gamma-aminobutyric acid (GABA) modulation of dopamine neurons in the ventral tegmental area (VTA). Changes in structural neuroplasticity can occur in GABAergic parvalbumin (PRV) positive neurons, which are enveloped by structures of the extracellular matrix called perineuronal nets (PNNs). In the current study, rats were trained to self-administer intravenous nicotine (0.03 mg/kg/infusion) for 21 days in 1-hour daily sessions with an incrementing fixed ratio requirement; a control group received saline infusions. At either 45 minutes or 72 hours after the last session, immunofluorescence measurements for PNNs, PRV and c-Fos were conducted. In VTA, nicotine self-administration reduced the number of PRV+ cells surrounded by PNNs at 45 minutes, as well as reducing the intensity of PNNs, suggesting a remodeling of GABA interneurons in this region; the number of PRV+ cells surrounded by PNNs was also reduced at 72 hours. A similar reduction of PNNs occurred in orbitofrontal cortex (OFC) but not in medial prefrontal cortex (prelimbic or infralimbic), 45 minutes after the last session; PNNs were not detected in nucleus accumbens (shell or core). The reduction of PNNs in VTA and OFC was unrelated to c-Fos + cells, as the percent of wisteria floribunda agglutinin + cells co-expressing c-Fos was decreased in OFC but not in VTA. Thus, nicotine self-administration remodeled PNNs surrounding GABA interneurons in VTA and its indirect connections to OFC, suggesting a new possible molecular target where nicotine-induced neuroplasticity takes place. PNN manipulations may prevent or reverse the different stages of tobacco addiction.
authors.affiliation: Department of Psychology and Center for Drug Abuse Research Translation (CDART), University of Kentucky, Lexington, KY, USA.
authors.forename: Dolores B
authors.initials: DB
authors.lastname: Vazquez-Sanroman
authors.affiliation: Centro de Investigaciones Cerebrales (CICE), Universidad Veracruzana Unidad de Ciencias de la Salud Xalapa, Veracruz, México, USA.
authors.forename: Reyna D
authors.initials: RD
authors.lastname: Monje
authors.affiliation: Department of Psychology and Center for Drug Abuse Research Translation (CDART), University of Kentucky, Lexington, KY, USA.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Bardo
mesh_terms: D000818:Animals; D005109:Extracellular Matrix / Q000187:drug effects; D005455:Fluorescent Antibody Technique; D005731:Ganglionic Stimulants / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D023421:Models, Animal; D009473:Neuronal Plasticity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects*; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology*; D017397:Prefrontal Cortex / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012646:Self Administration; D017557:Ventral Tegmental Area / Q000187:drug effects*
chemical_list: D005731:Ganglionic Stimulants; D009538:Nicotine
keywords: c-Fos; nicotine self-administration; orbitofrontal cortex (OFC); perineuronal nets (PNNs); ventral tegmental area (VTA)