Neuroplasticity transcript profile of the ventral striatum in the extinction of opioid-induced conditioned place preference

Hippocampal and amygdalar increased BDNF expression in the extinction of opioid-induced place preference

“…Two-way repeated measures ANOVA showed significant effects in time (CPP Phases: baseline, conditioning test, extinction test) and groups (sham-extinction, extinction, and extinction-resistant); main effect of time: F (1.5, 14) = 37; p < 0.0001; main effect of group: F ( Hedegaard et al, 2020 , Millan et al, 2011 ) = 9.5; p < 0.01; interaction: F ( Maglione et al, 2018 , Barker et al, 2015 ) = 3.6; p < 0.05. Like our previous findings ( Martínez-Rivera et al, 2019 ), results showed increased preference (CPP) for the morphine-paired side in all groups ( Fig. 1 B; Tukey post hoc; p’s < 0.01).…”

“…Several brain regions, including the VS/NAc, HPC, and AMY, among others, are involved in the extinction of behaviors related to addiction ( Goode and Maren, 2019 ). Our study provides continuity to previous molecular findings that implicates BDNF as a key player for extinction learning ( Andero and Ressler, 2012 , Cowansage et al, 2010 , Martínez-Rivera et al, 2019 ). In the present study we assessed relative BDNF expression in these brain regions, in animals that extinguished morphine CPP, as compared to animals receiving sham-extinction, or those that were extinction-resistant.…”

“…For this purpose, we have previously reported that the extinction of morphine-induced conditioned place preference (CPP) in rats, through receiving extinction training, displayed a different expression profile for synaptic plasticity genes of the ventral striatum/nucleus accumbens (VS/NAc), as compared with rats receiving withdrawal (i.e., forced abstinence in their home-cages). Particularly, our results showed a significant increase in brain derived neurotrophic factor (bdnf) mRNA in rats who successfully extinguished morphine CPP ( Martínez-Rivera et al, 2019 ), suggesting this neurotrophin as a potential molecular mediator for extinction of drug-associated conditioned stimuli. BDNF is a neurotrophic growth factor that has been linked to extinction processes in fear ( Rosas-Vidal et al, 2018 ) and drugs of abuse ( Bobadilla et al, 2019 , Castino et al, 2018 , Règue-Guyon et al, 2018 ).…”

“…Morphine sulfate (Sigma Aldrich, St. Louis MO; 5 mg/kg) was dissolved in saline (0.09%; 0.2 ml/100 g of body weight) and administered subcutaneously to all experimental groups. This dose of 5 mg/kg was chosen as previous studies found that it is sufficient to induce morphine-place preference without impacting mobility ( Martínez-Rivera et al, 2019 , Heinrichs et al, 2010 , Mueller et al, 2002 ), and able to elicit withdrawal-induced anxiety ( Zhang and Schulteis, 2008 ) , as demonstrated by them when a repetitive 5 mg/kg dose was administered by 4 days, resembling early stages of drug-dependence.…”

Aerobic exercise as a promising nonpharmacological therapy for the treatment of substance use disorders

“…Also, after an extinction session of 14 days of forced abstinence from heroin self‐administration, BDNF gene expression in the rat's medial prefrontal cortex and drug‐seeking behavior increased (Kuntz‐Melcavage et al., 2009); and mature‐ and pro‐BDNF expression increased after morphine withdrawal in the frontal cortex (Bachis et al., 2017; Peregud et al., 2020). In addition, BDNF mRNA or protein levels increased after extinction of morphine CPP or heroin withdrawal in the NAc of rats (Li et al., 2017; Martínez‐Rivera et al., 2019). Another group showed that a single infusion of BDNF into the VTA induced neurophysiological changes in the γ‐aminobutyric acid type A (GABAA) receptors of GABAergic neurons output signaling, from inhibitory to excitatory, leading to an opioid‐dependent state (Vargas‐Perez et al., 2009).…”