Identification of Benzodiazepine Use Based on Dried Blood Stains Analysis.

Biological matrices are typically used in forensic toxicological or pharmacological analysis: mainly blood, vitreous humor or urine. However, there are many cases in which crimes are a consequence of drug intoxication or drug abuse and they are not closed because over the months or years the samples become altered or decomposed. A dried blood stains test (DBS-MS) has recently been proposed to be used in drug toxicology when blood is found at a crime scene.

Cut-off value for β-trace protein (β-TP) as a rapid diagnostic of cerebrospinal fluid (CSF) leak detection.

Objective: To find an adequate cut-off point for beta trace protein (β-TP) in nasal secretion (NS) and validate this diagnostic test with a large sample of patients. Likewise, we evaluated β-TP test efficacy to confirm the cerebrospinal fluid (CSF) leakage closure after treatment.

Methods: We performed a retrospective analysis with 207 samples from 162 patients with suspected CSF leakage received in the Hospital Universitario Virgen de la Arrixaca between 2010 and 2016.

Upregulation of Heat-Shock Protein (hsp)-27 in a Patient with Heterozygous SPG11 c.1951C>T and SYNJ1 c.2614G>T Mutations Causing Clinical Spastic Paraplegia.

We report a 49-year-old patient suffering from spastic paraplegia with a novel heterozygous mutation and analyzed the levels of heat shock proteins (hsp)-27, dopamine (DA), and its metabolites in their cerebrospinal fluid (CSF). The hsp27 protein concentration in the patient's CSF was assayed by an ELISA kit, while DA levels and its metabolites in the CSF, 3,4-dihydroxyphenylacetic acid (DOPAC), Cys-DA, and Cys-DOPA were measured by HPLC. Whole exome sequencing demonstrated SPG-11 c.

Cardiac tyrosine hydroxylase activation and MB-COMT in dyskinetic monkeys.

The impact of age-associated disorders is increasing as the life expectancy of the population increments. Cardiovascular diseases and neurodegenerative disorders, such as Parkinson's disease, have the highest social and economic burden and increasing evidence show interrelations between them. Particularly, dysfunction of the cardiovascular nervous system is part of the dysautonomic symptoms of Parkinson's disease, although more studies are needed to elucidate the role of cardiac function on it.

Could Small Heat Shock Protein HSP27 Be a First-Line Target for Preventing Protein Aggregation in Parkinson's Disease?

Small heat shock proteins (HSPs), such as HSP27, are ubiquitously expressed molecular chaperones and are essential for cellular homeostasis. The major functions of HSP27 include chaperoning misfolded or unfolded polypeptides and protecting cells from toxic stress. Dysregulation of stress proteins is associated with many human diseases including neurodegenerative diseases, such as Parkinson's disease (PD).

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.

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.

Cardiac Noradrenaline Turnover and Heat Shock Protein 27 Phosphorylation in Dyskinetic Monkeys.

Background: Autonomic dysfunction is a well-known dominant symptom in the advanced stages of Parkinson's disease. However, the role of cardiac sympathetic nerves still needs to be elucidated.

Objectives: To evaluate cardiac sympathetic response in Parkinsonian and dyskinetic monkeys.

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.

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.

Development of Poly(lactide-co-glicolide) Nanoparticles Incorporating Morphine Hydrochloride to Prolong its Circulation in Blood.

Background: Formulations incorporating nanoparticles (NPs) are widely used to prolong drug release. In this regard, poly(lactide-co-glicolide) (PLGA) is often used in their preparation due to its high degree of biocompatibility and biodegradability. In the present study, morphine HCl is incorporated in PLGA-NPs and different preparation alternatives are evaluated for their effects on the properties, stability and capacity of encapsulation.

Expression of heat shock protein 27 and troponin T and troponin I after naloxone-precipitated morphine withdrawal.

Heat shock protein (Hsp27) renders cardioprotection from stress situations but little is known about its role in myofilaments. In this study we have evaluated the relationship between Hsp27 and troponin response after naloxone-induced morphine withdrawal. Rats were treated with two morphine (75 mg) pellets during six days.

CP-154,526 Modifies CREB Phosphorylation and Thioredoxin-1 Expression in the Dentate Gyrus following Morphine-Induced Conditioned Place Preference.

Corticotropin-releasing factor (CRF) acts as neuro-regulator of the behavioral and emotional integration of environmental and endogenous stimuli associated with drug dependence. Thioredoxin-1 (Trx-1) is a functional protein controlling the redox status of several proteins, which is involved in addictive processes. In the present study, we have evaluated the role of CRF1 receptor (CRF1R) in the rewarding properties of morphine by using the conditioned place preference (CPP) paradigm.

Crosstalk between G protein-coupled receptors (GPCRs) and tyrosine kinase receptor (TXR) in the heart after morphine withdrawal.

G protein-coupled receptors (GPCRs) comprise a large family of membrane receptors involved in signal transduction. These receptors are linked to a variety of physiological and biological processes such as regulation of neurotransmission, growth, and cell differentiation among others. Some of the effects of GPCRs are known to be mediated by the activation of mitogen-activated extracellular kinase (MAPK) pathways.

Role of corticotropin-releasing factor (CRF) receptor-1 on the catecholaminergic response to morphine withdrawal in the nucleus accumbens (NAc).

Stress induces the release of the peptide corticotropin-releasing factor (CRF) into the ventral tegmental area (VTA), and also increases dopamine (DA) levels in brain regions receiving dense VTA input. Since the role of stress in drug addiction is well established, the present study examined the possible involvement of CRF1 receptor in the interaction between morphine withdrawal and catecholaminergic pathways in the reward system. The effects of naloxone-precipitated morphine withdrawal on signs of withdrawal, hypothalamo-pituitary-adrenocortical (HPA) axis activity, dopamine (DA) and noradrenaline (NA) turnover in the nucleus accumbens (NAc) and activation of VTA dopaminergic neurons, were investigated in rats pretreated with vehicle or CP-154,526 (selective CRF1R antagonist).

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

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.

Pregabalin and topiramate regulate behavioural and brain gene transcription changes induced by spontaneous cannabinoid withdrawal in mice.

This study examined the actions of pregabalin and topiramate on behavioural and gene transcription alterations induced by spontaneous cannabinoid withdrawal in mice. Tolerance was induced in mice by administration of CP-55,940 (0.5 mg/kg/12 hours; i.

Restricted role of CRF1 receptor for the activity of brainstem catecholaminergic neurons in the negative state of morphine withdrawal.

Rationale: Evidence suggests that corticotropin-releasing factor (CRF) system is an important mediator in the negative symptoms of opioid withdrawal.

Objectives: We used genetically engineered mice lacking functional CRF receptor-1 (CRF1R) levels to study the role for CRF/CRF1R pathways in the negative affective states of opioid withdrawal.

Methods: Wild-type and CRF1R(-/-) offspring of CRF1R(+/-) breeders were identified by PCR analysis of tail DNA and were rendered dependent on morphine via intraperitoneal injection of increasing doses of morphine (10-60 mg/kg).

Tyrosine hydroxylase phosphorylation after naloxone-induced morphine withdrawal in the left ventricle.

Our previous studies have shown that morphine withdrawal induced hyperactivity of cardiac noradrenergic pathways. The purpose of the present study was to evaluate the effects of morphine withdrawal on site-specific tyrosine hydroxylase (TH) phosphorylation in the rat left ventricle. Dependence on morphine was induced by a 7-day s.

Tolerance to the antinociceptive effects of peripherally administered opioids. Expression of beta-arrestins.

Tolerance to peripheral antinociception after chronic exposure to systemic morphine was assessed in mice with chronic CFA-inflammation; cross-tolerance to locally administered mu, delta and kappa-opioid agonists and levels of beta-arrestins in the injured paw, were also evaluated. Tolerance was induced by the subcutaneous implantation of a 75 mg morphine-pellet, and antinociception evaluated with the Randall-Selitto test, 5 min after the subplantar injection of morphine, fentanyl, buprenorphine, DPDPE, U-50488H or CRF. Experiments were performed in the absence and presence of CFA-inflammation, in animals implanted with a morphine or placebo pellet.

Effects of chronic inflammation and morphine tolerance on the expression of phospho-ERK 1/2 and phospho-P38 in the injured tissue.

Opioids are used in humans in the treatment of chronic osteoarticular pain, but the development of tolerance to the analgesic effects after continuous administration is still not well understood. The aim of the present study was to evaluate the expression of phospho-ERK 1/2 and phospho-p38 in mice with monoarthritis chronically exposed to morphine as a possible explanation for the development of tolerance. Inflammation was induced by intraplantar injection of complete Freund's adjuvant (CFA) and the tolerance by implantation of 75 mg morphine pellets.

Differential involvement of 3', 5'-cyclic adenosine monophosphate-dependent protein kinase in regulation of Fos and tyrosine hydroxylase expression in the heart after naloxone induced morphine withdrawal.

We previously demonstrated that morphine withdrawal induced hyperactivity of the heart by the activation of noradrenergic pathways innervating the left and right ventricle, as evaluated by noradrenaline (NA) turnover and Fos expression. We investigated whether cAMP-dependent protein kinase (PKA) plays a role in this process by estimating changes in PKA immunoreactivity and the influence of inhibitor of PKA on Fos protein expression, tyrosine hydroxylase (TH) immunoreactivity levels and NA turnover in the left and right ventricle. Dependence on morphine was induced by a 7-day s.