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Yuanzhong Kai, Yanhua Li, Tingting Sun, Weiwei Yin, Yu Mao, Jie Li, Wen Xie, Shi Chen, Likui Wang, Juan Li, Zhi Zhang, Wenjuan Tao
Recent studies have shown that persistent pain facilitates the response to morphine reward. However, the circuit mechanism underlying this process remains ambiguous. In this study, using chronic constriction injury (CCI) of the sciatic nerve in mice, we found that persistent neuropathic pain reduced the minimum number of morphine conditioning sessions required to induce conditioned place preference (CPP) behavior. This dose of morphine had no effect on the pain threshold. In the medial prefrontal cortex (mPFC), which is involved in both pain and emotion processing, corticotropin-releasing factor (CRF) expressing neuronal activity was increased in CCI mice...
May 21, 2018: Translational Psychiatry
Jing Jing Li, Hanna Szkudlarek, Justine Renard, Roger Hudson, Walter Rushlow, Steven R Laviolette
Disturbances in prefrontal cortical (PFC) dopamine (DA) transmission are well-established features of psychiatric disorders involving pathological memory processing, such as post-traumatic stress disorder (PTSD) and opioid addiction. Transmission through PFC DA D4 receptors (D4R) has been shown to potentiate the emotional salience of normally non-salient emotional memories whereas transmission through PFC DA D1 receptors (D1R) has been demonstrated to selectively block recall of reward or aversion-related associative memories...
April 23, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Mahsaneh Vatankhah, Abdolrahman Sarihi, Alireza Komaki, Siamak Shahidi, Abbas Haghparast
Nucleus accumbens (NAc) plays plays a primary role in opioid reward. The actions of glutamate (which is the most extensive excitatory neurotransmitter in the mammalian central nervous system) are mediated through the activation of the ionotropic and metabotropic glutamate receptors (mGluRs). Previous studies have shown the extensive distributions of the different types of mGluRs, including mGluR7, in regions that are involved in opioid reward, such as NAc. In this study, CPP was used to investigate the effect of mGluR7 on the extinction period, and the reinstatement of morphine...
March 29, 2018: Brain Research Bulletin
Masayo Fujita, Soichiro Ide, Kazutaka Ikeda
A common notion is that essentially all addictive drugs, including opioids, activate dopaminergic pathways in the brain reward system, and the inappropriate use of such drugs induces drug dependence. However, an opioid reward response is reportedly still observed in several models of dopamine depletion, including in animals that are treated with dopamine blockers, animals that are subjected to dopaminergic neuron lesions, and dopamine-deficient mice. The intracranial self-stimulation response is enhanced by stimulants but reduced by morphine...
March 7, 2018: Annals of the New York Academy of Sciences
Magdalena Sustkova-Fiserova, Chrysostomos Charalambous, Tereza Havlickova, Marek Lapka, Pavel Jerabek, Nina Puskina, Kamila Syslova
The opioid-induced rise of extracellular dopamine, endocannabinoid anandamide and γ-aminobutyric acid (GABA) concentrations triggered by opioids in the nucleus accumbens shell (NACSh) most likely participate in opioid reward. We have previously demonstrated that systemic administration of ghrelin antagonist (JMV2959) significantly decreased morphine-induced dopamine and anandamide ( N -arachidonoylethanolamine, AEA) increase in the NACSh. Fentanyl is considered as a µ-receptor-selective agonist. The aim of this study was to test whether JMV2959, a growth hormone secretagogue receptor (GHS-R1A) antagonist, can influence the fentanyl-induced effects on anandamide, 2-arachidonoylglycerol (2-AG) and GABA in the NACSh and specify the involvement of GHS-R1A located in the ventral tegmental area (VTA) and nucleus accumbens (NAC)...
November 22, 2017: International Journal of Molecular Sciences
James Roland Markos, Hannah M Harris, Waseem Gul, Mahmoud A ElSohly, Kenneth J Sufka
This study sought to determine whether the cannabis constituent cannabidiol attenuates the development of morphine reward in the conditioned place preference paradigm. Separate groups of mice received either saline or morphine in combination with one of four doses of cannabidiol using three sets of drug/no-drug conditioning trials. After drug-place conditioning, morphine mice displayed robust place preference that was attenuated by 10 mg/kg cannabidiol. Further, when administered alone, this dose of cannabidiol was void of rewarding and aversive properties...
March 2018: Planta Medica
Wenli Mi, Shuxing Wang, Zerong You, Grewo Lim, Michael F McCabe, Hyangin Kim, Lucy Chen, Jianren Mao
BACKGROUND: Combination drug therapy is commonly used to treat chronic pain conditions such as neuropathic pain, and antidepressant is often used together with opioid analgesics. While rewarding is an intrinsic property of opioid analgesics, it is unknown whether the use of an antidepressant would influence opioid reward, which may contribute to opioid addiction. In this study, we examined whether nortriptyline (a tricyclic antidepressant and a first-line medication for neuropathic pain) would enhance the morphine rewarding property in both naive and chronic constriction sciatic nerve injury (CCI) rats...
September 2017: Anesthesia and Analgesia
Kenneth Blum, Mark S Gold, William Jacobs, William Vaughn McCall, Marcelo Febo, David Baron, Kristina Dushaj, Zsolt Demetrovics, Rajendra D Badgaiyan
This review begins with a comprehensive history of opioid dependence and treatment in the United States. The focus is an evidence-based treatment model for opioid/opiate dependent individuals. The role of reward genetic polymorphisms and the epigenetic modifications that lead to vulnerability to use and misuse of opiates/opioid to treat pain are reviewed. The neurochemical mechanisms of acute opiate withdrawal and opiate/opioid reward mechanisms are explored with a goal of identifying specific treatment targets...
March 1, 2017: Frontiers in Bioscience (Landmark Edition)
Kendra L Kobrin, Danielle T Arena, Stephen C Heinrichs, Olivia H Nguyen, Gary B Kaplan
The dopamine D1 receptor (D1R) has a role in opioid reward and conditioned place preference (CPP), but its role in CPP extinction is undetermined. We examined the effect of D1R agonist SKF81297 on the extinction of opioid CPP and associated dendritic morphology in the nucleus accumbens (NAc), a region involved with reward integration and its extinction. During the acquisition of morphine CPP, mice received morphine and saline on alternate days; injections were given immediately before each of eight daily conditioning sessions...
March 30, 2017: Behavioural Brain Research
Padmanabhan Mannangatti, Santhanalakshmi Sundaramurthy, Sammanda Ramamoorthy, Lankupalle D Jayanthi
RATIONALE: Neurokinin-1 receptor (NK1R) signaling modulates behaviors associated with psychostimulants and opioids. Psychostimulants, such as amphetamine (AMPH) and cocaine, bind to monoamine transporters and alter their functions. Both dopamine and norepinephrine transporters are regulated by NK1R activation suggesting a role for NK1R mediated catecholamine transporter regulation in psychostimulant-mediated behaviors. OBJECTIVES: The effect of in vivo administration of aprepitant (10 mg/kg) on the expression of AMPH (0...
February 2017: Psychopharmacology
Xiao-Fei Wang, Elisabeth Barbier, Yi-Ting Chiu, Yi He, Jia Zhan, Guo-Hua Bi, Hai-Ying Zhang, Bo Feng, Lee-Yuan Liu-Chen, Jia Bei Wang, Zheng-Xiong Xi
The etiology and pathophysiology underlying opioid tolerance and dependence are still unknown. Because mu opioid receptor (MOR) plays an essential role in opioid action, many vulnerability-related studies have focused on single nucleotide polymorphisms of MOR, particularly on A118G. In this study, we found that a single-point mutation at the MOR T394 phosphorylation site could be another important susceptive factor in the development of opioid tolerance and dependence in mice. T394A mutation, in which a threonine at 394 was replaced by an alanine, did not alter agonist binding to MOR and opioid analgesia, but resulted in loss of etorphine-induced MOR internalization in spinal dorsal horn neurons and opioid analgesic tolerance induced by either morphine or etorphine...
October 5, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Tuan Trang, Ream Al-Hasani, Daniela Salvemini, Michael W Salter, Howard Gutstein, Catherine M Cahill
UNLABELLED: Treating pain is one of the most difficult challenges in medicine and a key facet of disease management. The isolation of morphine by Friedrich Sertürner in 1804 added an essential pharmacological tool in the treatment of pain and spawned the discovery of a new class of drugs known collectively as opioid analgesics. Revered for their potent pain-relieving effects, even Morpheus the god of dreams could not have dreamt that his opium tincture would be both a gift and a burden to humankind...
October 14, 2015: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Catherine E Myers, Jony Sheynin, Tarryn Balsdon, Andre Luzardo, Kevin D Beck, Lee Hogarth, Paul Haber, Ahmed A Moustafa
Addiction is the continuation of a habit in spite of negative consequences. A vast literature gives evidence that this poor decision-making behavior in individuals addicted to drugs also generalizes to laboratory decision making tasks, suggesting that the impairment in decision-making is not limited to decisions about taking drugs. In the current experiment, opioid-addicted individuals and matched controls with no history of illicit drug use were administered a probabilistic classification task that embeds both reward-based and punishment-based learning trials, and a computational model of decision making was applied to understand the mechanisms describing individuals' performance on the task...
January 1, 2016: Behavioural Brain Research
Emanuela Mhillaj, Maria G Morgese, Paolo Tucci, Maria Bove, Stefania Schiavone, Luigia Trabace
Androgens are mainly prescribed to treat several diseases caused by testosterone deficiency. However, athletes try to promote muscle growth by manipulating testosterone levels or assuming androgen anabolic steroids (AAS). These substances were originally synthesized to obtain anabolic effects greater than testosterone. Although AAS are rarely prescribed compared to testosterone, their off-label utilization is very wide. Furthermore, combinations of different steroids and doses generally higher than those used in therapy are common...
2015: Frontiers in Neuroscience
Ethan M Anderson, Turi Reeves, Katherine Kapernaros, John K Neubert, Robert M Caudle
Opioid withdrawal causes a dysphoric state that can lead to complications in pain patients and can propagate use in drug abusers and addicts. Opioid withdrawal changes the activity of neurons in the nucleus accumbens, an area rich in both opioid-binding mu opioid receptors and glutamate-binding NMDA receptors. Because the accumbens is an area important for reward and aversion, plastic changes in this area during withdrawal could alter future behaviors in animals. We discovered an increase in phosphorylation of serine 897 in the NR1 subunit of the NMDA receptor (pNR1) during acute morphine withdrawal...
December 2015: Journal of Pharmacology and Experimental Therapeutics
Tuğçe Uskur, M Aydın Barlas, A Gökhan Akkan, Andleeb Shahzadi, Tayfun Uzbay
Dexmedetomidine (DEX) is an alpha-2 adrenergic agonist drug recently introduced to anesthesia practice. Certain agents used in anesthesia practice have been associated with abuse and addiction problems; however, few studies have investigated the role of DEX on addictive processes. Here, the effects and possible mechanisms of action of DEX on conditioned place preference (CPP), a model used for measuring the rewarding effects of drug abuse in rats, was investigated. The CPP apparatus was considered "biased" as the animals preferred the grid side to the mesh side...
January 1, 2016: Behavioural Brain Research
Jacinta L Johnson, Yuen H Kwok, Nicole M Sumracki, James E Swift, Mark R Hutchinson, Kirk Johnson, Desmond B Williams, Jonathon Tuke, Paul E Rolan
BACKGROUND: Medication overuse headache (MOH) is a condition bordering between a chronic pain condition and a substance dependence disorder. Activation of immunocompetent glial cells in the central nervous system has been linked to both pathological pain and drug addiction/reward. Preclinically, ibudilast attenuates glial activation and is able to reduce neuropathic pain and markers of substance dependence. We therefore hypothesized ibudilast would reduce headache burden and opioid analgesic requirements in patients with opioid overuse headache...
October 2015: Headache
Laurie P Sutton, Olga Ostrovskaya, Maria Dao, Keqiang Xie, Cesare Orlandi, Roy Smith, Sunmee Wee, Kirill A Martemyanov
BACKGROUND: Morphine mediates its euphoric and analgesic effects by acting on the μ-opioid receptor (MOR). MOR belongs to the family of G-protein coupled receptors whose signaling efficiency is controlled by the regulator of G-protein signaling (RGS) proteins. Our understanding of the molecular diversity of RGS proteins that control MOR signaling, their circuit specific actions, and underlying cellular mechanisms is very limited. METHODS: We used genetic approaches to ablate regulator of G-protein signaling 7 (RGS7) both globally and in specific neuronal populations...
August 1, 2016: Biological Psychiatry
Michael A Emery, M L Shawn Bates, Paul J Wellman, Shoshana Eitan
BACKGROUND: Opioids alter the responses of D2-like dopamine receptors (D2DRs), known to be involved in the pathology of addiction and other mental illnesses. Importantly, our recent results demonstrated that various opioids differentially modulate the behavioral responses of D2DRs. OBJECTIVE: To examine the effect of various opioids on striatal activation levels of Akt and ERK1/2, as well as the signaling responses of D2DRs following opioid exposure. METHODS: Mice were pre-treated with 20 mg/kg morphine, hydrocodone, oxycodone, or saline for 6 days...
May 1, 2016: Pain Medicine: the Official Journal of the American Academy of Pain Medicine
Ream Al-Hasani, Jordan G McCall, Gunchul Shin, Adrian M Gomez, Gavin P Schmitz, Julio M Bernardi, Chang-O Pyo, Sung Il Park, Catherine M Marcinkiewcz, Nicole A Crowley, Michael J Krashes, Bradford B Lowell, Thomas L Kash, John A Rogers, Michael R Bruchas
The nucleus accumbens (NAc) and the dynorphinergic system are widely implicated in motivated behaviors. Prior studies have shown that activation of the dynorphin-kappa opioid receptor (KOR) system leads to aversive, dysphoria-like behavior. However, the endogenous sources of dynorphin in these circuits remain unknown. We investigated whether dynorphinergic neuronal firing in the NAc is sufficient to induce aversive behaviors. We found that photostimulation of dynorphinergic cells in the ventral NAc shell elicits robust conditioned and real-time aversive behavior via KOR activation, and in contrast, photostimulation of dorsal NAc shell dynorphin cells induced a KOR-mediated place preference and was positively reinforcing...
September 2, 2015: Neuron
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