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 GABA modulation of dopamine (DA) 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 IV nicotine (0.03 mg/kg/infusion) for 21 days in 1-h daily sessions with an incrementing fixed ratio requirement; a control group received saline infusions. At either 45 min or 72 hr 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 min, 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 hr. A similar reduction of PNNs occurred in orbitofrontal cortex (OFC), but not in medial prefrontal cortex (PrL or IL), 45 min 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 WFA+ 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.

Early life trauma increases threat response of peri‐weaning rats, reduction of axo‐somatic synapses formed by parvalbumin cells and perineuronal net in the basolateral nucleus of amygdala

“…PNN intensity is frequently used as a proxy for maturity (Carulli, Foscarin, Faralli, Pajaj, & Rossi, ; Chen, He, & Lasek, ; Foscarin et al, ; Happel & Frischknecht, ; Slaker et al, ; Vazquez‐Sanroman, Monje, & Bardo, ). Thus, the lighter intensity of SAM brains' PNN at PN23 could also indicate reduced PNN maturity.…”

“…PNN intensity is frequently used as a proxy for maturity (Foscarin et al, 2011; Carulli et al, 2013; Chen et al, 2015; Slaker et al, 2015; Happel and Frischknecht, 2016; Vazquez-Sanroman et al, 2016). Thus, the lighter intensity of SAM brains’ PNN at PN23 could also indicate reduced PNN maturity.…”

Releasing Addiction Memories Trapped in Perineuronal Nets

“…This reduction was normalized after cue-induced reinstatement of heroin self-administration. For nicotine, the number and intensity of PNNs surrounding parvalbumin-expressing neurons were decreased in the ventral tegmental area (VTA) and the orbitofrontal cortex (a region of the prefrontal cortex) forty-five minutes after a nicotine self-administration session [63]. The reduction in the number of PNNs in the VTA was maintained at seventy-two hours after the last self-administration session [63].…”

Comparative analysis of the modulation of perineuronal nets in the prefrontal cortex of rats during protracted withdrawal from cocaine, heroin and sucrose self-administration

“…) withdrawal from nicotine(Vazquez-Sanroman et al, 2017). However, another experiment showed that PNNs decreased in the medial prefrontal cortex after protracted (21 days) withdrawal from heroin(Van den Oever et al, 2010).…”