Dopamine D3 Receptor Modulates Akt/mTOR and ERK Pathways Differently during the Reinstatement of Cocaine-Seeking Behavior Induced by Psychological versus Physiological Stress.

Stress triggers relapses in cocaine use that engage the activity of memory-related nuclei, such as the basolateral amygdala (BLA) and dentate gyrus (DG). Preclinical research suggests that D3 receptor (D3R) antagonists may be a promising means to attenuate cocaine reward and relapse. As D3R regulates the activity of the Akt/mTOR and MEK/ERK pathways, we assessed the effects of SB-277011-A, a D3R antagonist, on the activity of these kinases during the reinstatement of cocaine-induced conditioned place preference (CPP) induced by psychological (restraint) and physiological (tail pinch) stress.

Molecular Mechanisms Underlying the Retrieval and Extinction of Morphine Withdrawal-Associated Memories in the Basolateral Amygdala and Dentate Gyrus.

Despite their indisputable efficacy for pain management, opiate prescriptions remain highly controversial partially due to their elevated addictive potential. Relapse in drug use is one of the principal problems for addiction treatment, with drug-associated memories being among its main triggers. Consequently, the extinction of these memories has been proposed as a useful therapeutic tool.

Distinct Regulation of Dopamine D3 Receptor in the Basolateral Amygdala and Dentate Gyrus during the Reinstatement of Cocaine CPP Induced by Drug Priming and Social Stress.

Relapse in the seeking and intake of cocaine is one of the main challenges when treating its addiction. Among the triggering factors for the recurrence of cocaine use are the re-exposure to the drug and stressful events. Cocaine relapse engages the activity of memory-related nuclei, such as the basolateral amygdala (BLA) and the hippocampal dentate gyrus (DG), which are responsible for emotional and episodic memories.

Barriers and Facilitators to Implementing Bundled Acupuncture and Yoga Therapy to Treat Chronic Pain in Community Healthcare Settings: A Feasibility Pilot.

To identify factors associated with implementing bundled group acupuncture and yoga therapy (YT) to treat underserved patients with chronic pain in community health center (CHC) settings. This is not an implementation science study, but rather an organized approach for identification of barriers and facilitators to implementing these therapies as a precursor to a future implementation science study. This study was part of a single-arm feasibility trial, which aimed to test the feasibility of bundling GA and YT for chronic pain in CHCs.

Naloxone-induced conditioned place aversion score and extinction period are higher in C57BL/6J morphine-dependent mice than in Swiss: Role of HPA axis.

Intense associative memories develop between drug-paired contextual cues and the drug withdrawal associated aversive feeling. They have been suggested to contribute to the high rate of relapse. Our study was aimed to elucidate the involvement of hypothalamic-pituitary-adrenocortical (HPA) axis activity in the expression and extinction of aversive memory in Swiss and C57BL/6J (B6) mice.

Group Acupuncture Therapy With Yoga Therapy for Chronic Neck, Low Back, and Osteoarthritis Pain in Safety Net Setting for an Underserved Population: Design and Rationale for a Feasibility Pilot.

Chronic pain is prevalent in the United States, with impact on physical and psychological functioning as well as lost work productivity. Minority and lower socioeconomic populations have increased prevalence of chronic pain with less access to pain care, poorer outcomes, and higher risk of fatal opioid overdose. Acupuncture therapy is effective in treating chronic pain conditions including chronic low back pain, neck pain, shoulder pain, and knee pain from osteoarthritis.

Blockade of D3 receptor prevents changes in DAT and D3R expression in the mesolimbic dopaminergic circuit produced by social stress- and cocaine prime-induced reinstatement of cocaine-CPP.

Background: Cocaine may cause persistent changes in the brain, which are more apparent in DA transporter (DAT) and DA receptor availability within the nucleus accumbens (NAc). On the other hand, the DA D3 receptor (D3R) has emerged as a promising pharmacotherapeutic target for substance use disorders.

Aims: This study aims to assess the impact of selective D3R antagonism on DAT and D3R after reinstatement of cocaine preference (CPP) induced by an acute session of social defeat stress (SDS) and a cocaine prime in mice after a period of abstinence.

Unraveling the molecular mechanisms involved in alcohol intake and withdrawal in adolescent mice exposed to alcohol during early life stages.

Alcohol interferes with foetal development and prenatal alcohol exposure can lead to adverse effects known as foetal alcohol spectrum disorders. We aimed to assess the underlying neurobiological mechanisms involved in alcohol intake and withdrawal in adolescent mice exposed to alcohol during early life stages, in discrete brain areas. Pregnant C57BL/6 female mice were exposed to binge alcohol drinking from gestation to weaning.

Cardiac Protective Role of Heat Shock Protein 27 in the Stress Induced by Drugs of Abuse.

Heat shock proteins (HSP) are induced after different stress situations. Some of these proteins, particularly HSP-27, function as markers to indicate cellular stress or damage and protect the heart during addictive processes. Morphine withdrawal induces an enhancement of sympathetic activity in parallel with an increased HSP-27 expression and phosphorylation, indicating a severe situation of stress.

Liposome-Encapsulated Morphine Affords a Prolonged Analgesia While Facilitating Extinction of Reward and Aversive Memories.

Morphine is thoroughly used for pain control; however, it has a high addictive potential. Opioid liposome formulations produce controlled drug release and have been thoroughly tested for pain treatment although their role in addiction is still unknown. This study investigated the effects of free morphine and morphine encapsulated in unilamellar and multilamellar liposomes on antinociception and on the expression and extinction of the positive and negative memories associated with environmental cues.

Conditioned aversive memory associated with morphine withdrawal increases brain-derived neurotrophic factor in dentate gyrus and basolateral amygdala.

Morphine has been shown to increase the expression of brain-derived neurotrophic factor (BDNF) in the brain. However, little is known about the effect of conditioned naloxone-precipitated morphine withdrawal on BDNF and its precursor protein, proBDNF. We used the conditioned place aversion (CPA) paradigm to evaluate the role of corticotropin-releasing factor (CRF)/CRF1 receptor signaling on the BDNF expression and corticosterone plasma levels after CPA expression and extinction.

Pharmacological modulation of the behavioral effects of social defeat in memory and learning in male mice.

Rationale: Previous studies have demonstrated that repeated social defeat (RSD) stress only induces cognitive deficits when experienced during adulthood. However, RSD increases cocaine-rewarding effects in adult and adolescent mice, inducing different expressions of proBDNF in the ventral tegmental area.

Objective: The aim of the present study was to evaluate the effect of cocaine administration in socially defeated adult or adolescent mice on learning, memory, and anxiety.

Role of glucocorticoids on noradrenergic and dopaminergic neurotransmission within the basolateral amygdala and dentate gyrus during morphine withdrawal place aversion.

Aversive memories related to drug withdrawal can generate a motivational state leading to compulsive drug taking. However, the mechanisms underlying the generation of these withdrawal memories remain unclear. Limbic structures, such as the basolateral amygdala (BLA) and the dentate gyrus (DG) of the hippocampus, play a crucial role in the negative affective component of morphine withdrawal.

Binge ethanol and MDMA combination exacerbates HSP27 and Trx-1 (biomarkers of toxic cardiac effects) expression in right ventricle.

Aims: Oxidative stress caused by exposure to drugs of abuse such as ethanol or 3, 4 methylenedioxymethamphetamine (MDMA) may derive from direct or indirect effects in many organs including the heart. The aim of the present work was to evaluate cardiac sympathetic activity and the expression and activation of two antioxidant proteins: heat shock protein27 (HSP27) and thioredoxin-1 (Trx-1) after voluntary binge ethanol consumption, alone and in combination with MDMA.

Material And Methods: Adolescent mice received MDMA, ethanol or both.

Modulation of stress- and cocaine prime-induced reinstatement of conditioned place preference after memory extinction through dopamine D3 receptor.

Accumulating evidence indicates that dopamine (DA) D3 receptor (DAD3R) antagonists appear highly promising in attenuating cocaine reward and relapse in preclinical models of addiction. In the present study, we investigated the effects of the selective DAD3R antagonist SB-277011-A on the reinstatement of cocaine-induced conditioned place preference (CPP) produced by a priming dose of cocaine, by social defeat stress and by two kinds of physiological stressors (restraint and tail pinch) in male adult mice. We also explored reinstatement-related plasma corticosterone levels (as marker of stress response) and the effects of blocking DAD3R.

Distinct regulation pattern of Egr-1, BDNF and Arc during morphine-withdrawal conditioned place aversion paradigm: Role of glucocorticoids.

Negative affective aspects of opiate abstinence contribute to the persistence of substance abuse. Importantly, interconnected brain areas involved in aversive motivational processes, such as the ventral tegmental area (VTA) and medial prefrontal cortex (mPFC), become activated when animals are confined to withdrawal-paired environments. In the present study, place aversion was elicited in sham and adrenalectomized (ADX) animals by conditioned naloxone-precipitated drug withdrawal following exposure to chronic morphine.

The involvement of CRF1 receptor within the basolateral amygdala and dentate gyrus in the naloxone-induced conditioned place aversion in morphine-dependent mice.

Drug withdrawal-associated aversive memories trigger relapse to drug-seeking behavior. Corticotrophin-releasing factor (CRF) is an important mediator of the reinforcing properties of drugs of abuse. However, the involvement of CRF1 receptor (CRF1R) in aversive memory induced by opiate withdrawal has yet to be elucidated.

Repeated social defeat and the rewarding effects of cocaine in adult and adolescent mice: dopamine transcription factors, proBDNF signaling pathways, and the TrkB receptor in the mesolimbic system.

Rationale: Repeated social defeat (RSD) increases the rewarding effects of cocaine in adolescent and adult rodents.

Objective: The aim of the present study was to compare the long-term effects of RSD on the conditioned rewarding effects of cocaine and levels of the transcription factors Pitx3 and Nurr1 in the ventral tegmental area (VTA), the dopamine transporter (DAT), the D2 dopamine receptor (D2DR) and precursor of brain-derived neurotrophic factor (proBDNF) signaling pathways, and the tropomyosin-related kinase B (TrkB) receptor in the nucleus accumbens (NAc) in adult and adolescent mice.

Methods: Male adolescent and young adult OF1 mice were exposed to four episodes of social defeat and were conditioned 3 weeks later with 1 mg/kg of cocaine.

Maternal Separation Impairs Cocaine-Induced Behavioural Sensitization in Adolescent Mice.

Adverse early-life conditions induce persistent disturbances that give rise to negative emotional states. Therefore, early life stress confers increased vulnerability to substance use disorders, mainly during adolescence as the brain is still developing. In this study, we investigated the consequences of maternal separation, a model of maternal neglect, on the psychotropic effects of cocaine and the neuroplasticity of the dopaminergic system.

Glucocorticoid Homeostasis in the Dentate Gyrus Is Essential for Opiate Withdrawal-Associated Memories.

Drug-withdrawal-associated aversive memories might trigger relapse to drug-seeking behavior. However, changes in structural and synaptic plasticity, as well as epigenetic mechanisms, which may be critical for long-term aversive memory, have yet to be elucidated. We used male Wistar rats and performed conditioned-place aversion (CPA) paradigm to uncover the role of glucocorticoids (GCs) on plasticity-related processes that occur within the dentate gyrus (DG) during opiate-withdrawal conditioning (memory formation-consolidation) and after reactivation by re-exposure to the conditioned environment (memory retrieval).

Different contribution of glucocorticoids in the basolateral amygdala to the formation and expression of opiate withdrawal-associated memories.

Drug-withdrawal aversive memories generate a motivational state leading to compulsive drug taking, with plasticity changes in the basolateral amygdala (BLA) being essential in aversive motivational learning. The conditioned-place aversion (CPA) paradigm allows for measuring the negative affective component of drug withdrawal. First, CPA triggers association between negative affective consequences of withdrawal with context (memory consolidation).

Acute Morphine, Chronic Morphine, and Morphine Withdrawal Differently Affect Pleiotrophin, Midkine, and Receptor Protein Tyrosine Phosphatase β/ζ Regulation in the Ventral Tegmental Area.

Pleiotrophin (PTN) and midkine (MK) are secreted growth factors and cytokines, proposed to be significant neuromodulators with multiple neuronal functions. PTN and MK are generally related with cell proliferation, growth, and differentiation by acting through different receptors. PTN or MK, signaling through receptor protein tyrosine phosphatase β/ζ (RPTPβ/ζ), lead to the activation of extracellular signal-regulated kinases (ERKs) and thymoma viral proto-oncogene (Akt), which induce morphological changes and modulate addictive behaviors.

Glucocorticoid receptor but not mineralocorticoid receptor mediates the activation of ERK pathway and CREB during morphine withdrawal.

Recent research suggests that glucocorticoids are involved in the development of addiction to drugs of abuse. They share this role with dopamine (DA), and with different signalling pathways and/or transcription factors such as extracellular-signal regulated kinases (ERK) and cAMP response element binding protein (CREB). However, the relation between them is not completely elucidated.