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

• Published in: Neurobiology of learning and memory Vol. 163; p. 107031
• Main Authors: Martínez-Rivera, Freddyson J., Martínez, Namyr A., Martínez, Magdiel, Ayala-Pagán, Roxsana N., Silva, Walter I., Barreto-Estrada, Jennifer L.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.2019
• Subjects: Analgesics, Opioid - pharmacology; Animals; Bdnf; Conditioned place preference; Conditioning, Classical - drug effects; Extinction, Psychological; Genes; Learning; Male; Morphine; Morphine - pharmacology; Neuronal Plasticity - drug effects; Nucleus Accumbens - drug effects; Nucleus Accumbens - metabolism; Rats; Rats, Sprague-Dawley; Real-Time Polymerase Chain Reaction; Receptors, Opioid - drug effects; Receptors, Opioid - metabolism; Reward; Transcriptome - drug effects; Ventral Striatum - drug effects; Ventral Striatum - metabolism; Learning; Morphine; Reward; Conditioned place preference; Bdnf; Genes
• ISSN: 1074-7427; 1095-9564; 1095-9564
• DOI: 10.1016/j.nlm.2019.107031

•Extinction learning induced Bdnf upregulation in the ventral striatum.•Extinction resistance was associated with selective gene targets.•Extinction training counteracts the withdrawal-associated plasticity.•The lack of extinction training induced a widespread modulation of genes. Persistent drug-seeking behavior has been associated with deficits in neural circuits that regulate the extinction of addictive behaviors. Although there is extensive data that associates addiction phases with neuroplasticity changes in the reward circuit, little is known about the underlying mechanisms of extinction learning of opioid associated cues. Here, we combined morphine-conditioned place preference (CPP) with real-time polymerase chain reaction (RT-PCR) to identify the effects of extinction training on the expression of genes (mRNAs) associated with synaptic plasticity and opioid receptors in the ventral striatum/nucleus accumbens (VS/NAc). Following morphine extinction training, we identified two animal subgroups showing either extinction (low CPP) or extinction-resistance (high CPP). A third group were conditioned to morphine but did not receive extinction training (sham-extinction; high CPP). RT-PCR results showed that brain derived neurotrophic factor (Bdnf) was upregulated in rats showing successful extinction. Conversely, the lack of extinction training (sham-extinction) upregulated genes associated with kinases (Camk2g), neurotrophins (Ngfr), synaptic connectivity factors (Ephb2), glutamate neurotransmission (Grm8) and opioid receptors (μ1, Δ1). To further identify genes modulated by morphine itself, comparisons with their saline-counterparts were performed. Results revealed that Bdnf was consistently upregulated in the extinction group. Alternatively, widespread gene modulation was observed in the group with lack of extinction training (i.e. Drd2, Cnr1, Creb, μ1, Δ1) and the group showing extinction resistance (i.e. Crem, Rheb, Tnfa). Together, our study builds on the identification of putative genetic markers for the extinction learning of drug-associated cues.