Accumbal dopamine, noradrenaline and serotonin activity after naloxone-conditioned place aversion in morphine-dependent mice

• Published in: Neurochemistry international 2012-08, Vol.61 (3), p.433-440
• Main Authors: Gómez-Milanés, Iván, Almela, Pilar, García-Carmona, Juan-Antonio, Salud García-Gutiérrez, M., Aracil-Fernández, Auxiliadora, Manzanares, Jorge, Victoria Milanés Maquilón, M., Luisa Laorden, M.
• Format: Article
• Language: English
• Subjects: Analgesics; Animals; Aversion; Avoidance Learning; Biological and medical sciences; Blotting, Western; Chromatography, High Pressure Liquid; Conditioned place aversion; Conditioning, Operant; Dopamine; Dopamine - metabolism; Drug dependence; Fundamental and applied biological sciences. Psychology; Gene expression; Gene regulation; High-performance liquid chromatography; Male; Medical sciences; Mice; Morphine; Morphine - administration & dosage; Motivation; Naloxone; Naloxone - pharmacology; Neuropharmacology; Noradrenaline; Norepinephrine; Norepinephrine - metabolism; Nucleus accumbens; Nucleus Accumbens - metabolism; Opioids; Pharmacology. Drug treatments; Phosphorylation; Polymerase chain reaction; Post-transcription; Real-Time Polymerase Chain Reaction; Reinforcement; Serotonin; Serotonin - metabolism; TH expression; TH phosphorylation; Tyrosine 3-monooxygenase; Tyrosine 3-Monooxygenase - genetics; Tyrosine 3-Monooxygenase - metabolism; Vertebrates: nervous system and sense organs; Western blotting
• ISSN: 0197-0186; 1872-9754
• DOI: 10.1016/j.neuint.2012.06.011

► We evaluate the role of monoamines in naloxone-induced conditioned place aversion (CPA). ► We examined changes in the turnover of DA, NA and 5-HT in the nucleus accumbens (NAc). ► We examine the changes in TH mRNA in the ventral tegmental area (VTA). ► Morphine withdrawal Increases NA and DA turnover in NAc and elevates TH expression in VTA. ► CPA is related to NA and DA activity and transcriptional regulation of TH. Dopamine (DA) neurons not only show a pattern signaling the magnitude, delay and probability of rewards but also code negative motivation and aversive events. Beside DA, other systems such as noradrenaline (NA) and serotonin (5-HT) may also be implicated in naloxone-induced conditioned place aversion (CPA; an index of the aversive consequences of withdrawal). The purpose of the present study was to evaluate: (i) the turnover of DA, NA and 5-HT in the nucleus accumbens (NAc), one of the most important substrates for aversive states, (ii) the changes in tyrosine hydroxylase (TH) gene expression in the ventral tegmental area, and (iii) total TH protein levels and TH phosphorylation in the NAc after naloxone-induced morphine withdrawal. DA, NA and 5-HT turnover was evaluated by high-performance liquid chromatography (HPLC). TH gene expression was determined by real time quantitative PCR (RT-PCR) and total TH and TH phosphorylated at Ser31 and Ser40 were analyzed by Western blot. Present results show that the aversion for environmental cues paired with opioid withdrawal was higher than that observed in the saline group treated with naloxone, which indicates that morphine pretreatment potentiated the ability of naloxone to produce place aversion. In addition, present data show that naloxone-induced CPA positively correlated with an increase of DA and NA turnover in the NAc, which paralleled an increase in TH gene expression in the VTA and TH phosphorylation and enhanced TH protein levels in the NAc. Thus, the present study indicates that naloxone-induced aversion in morphine-dependent mice enhances DA and NA activity in the NAc and suggests that transcriptional and post-transcriptional regulation of TH could be involved in the hyperactivity of mesolimbic dopaminergic system observed in morphine-withdrawn mice.