Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction

The self-medication hypothesis of addictive disorders derives primarily from clinical observations of patients with substance use disorders. Individuals discover that the specific actions or effects of each class of drugs relieve or change a range of painful affect states. Self-medication factors occur in a context of self-regulation vulnerabilities--primarily difficulties in regulating affects, self-esteem, relationships, and self-care. Persons with substance use disorders suffer in the extreme with their feelings, either being overwhelmed with painful affects or seeming not to feel their emotions at all. Substances of abuse help such individuals to relieve painful affects or to experience or control emotions when they are absent or confusing. Diagnostic studies provide evidence that variously supports and fails to support a self-medication hypothesis of addictive disorders. The cause-consequence controversy involving psychopathology and substance use/abuse is reviewed and critiqued. In contrast, clinical observations and empirical studies that focus on painful affects and subjective states of distress more consistently suggest that such states of suffering are important psychological determinants in using, becoming dependent upon, and relapsing to addictive substances. Subjective states of distress and suffering involved in motives to self-medicate with substances of abuse are considered with respect to nicotine dependence and to schizophrenia and posttraumatic stress disorder comorbid with a substance use disorder.

The Self-medication Hypothesis of Substance Use Disorders: A Reconsideration and Recent Applications

Three hard winter wheat varieties (Akron, Trego, and Platte) were examined and compared for their free radical scavenging properties and total phenolic contents (TPC) Free radical scavenging properties of wheat grain extracts were evaluated by spectrophotometric and electron spin resonance (ESR) spectrometry methods against stable 2,2-diphenyl-1-picryhydrazyl radical (DPPH*) and radical cation ABTS*+ (2,2'-azino-di[3-ethylbenzthiazoline sulfonate]) The results showed that the three wheat extracts differed in their capacities to quench or inhibit DPPH* and ABTS*+ Akron showed the greatest activity to quench DPPH radicals, while Platte had the highest capacity against ABTS*+ The ED50 values of wheat extracts against DPPH radicals were 060 mg/mL for Akron, 71 mg/mL for Trego, and 095 mg/mL for Platte under the experimental conditions The trolox equivalents against ABTS*+ were 131 +/- 044, 108 +/- 005, and 191 +/- 006 micromol/g of grain for Akron, Trego, and Platte wheat, respectively ESR results confirmed that wheat extracts directly reacted with and quenched free radicals The TPC were 4879 +/- 9278 microg gallic acid equivalents/g of grain No correlation was observed between TPC and radical scavenging capacities for DPPH* and ABTS*+ (p = 015 and p > 05, respectively)

Free radical scavenging properties of wheat extracts.

Free radicals are highly reactive molecules implicated in the pathology of traumatic brain injury and cerebral ischemia, through a mechanism known as oxidative stress. After brain injury, reactive oxygen and reactive nitrogen species may be generated through several different cellular pathways, including calcium activation of phospholipases, nitric oxide synthase, xanthine oxidase, the Fenton and Haber-Weiss reactions, by inflammatory cells. If cellular defense systems are weakened, increased production of free radicals will lead to oxidation of lipids, proteins, and nucleic acids, which may alter cellular function in a critical way. The study of each of these pathways may be complex and laborious since free radicals are extremely short-lived. Recently, genetic manipulation of wild-type animals has yielded species that over- or under-express genes such as, copper-zinc superoxide dismutase, manganese superoxide dismutase, nitric oxide synthase, and the Bcl-2 protein. The introduction of the species has improved the understanding of oxidative stress. We conclude here that substantial experimental data links oxidative stress with other pathogenic mechanisms such as excitotoxicity, calcium overload, mitochondrial cytochrome c release, caspase activation, and apoptosis in central nervous system (CNS) trauma and ischemia, and that utilization of genetically manipulated animals offers a unique possibility to elucidate the role of free radicals in CNS injury in a molecular fashion.

Free Radical Pathways in CNS Injury

Opioid receptors have been targeted for the treatment of pain and related disorders for thousands of years and remain the most widely used analgesics in the clinic. Mu (μ), kappa (κ), and delta (δ) opioid receptors represent the originally classified receptor subtypes, with opioid receptor like-1 (ORL1) being the least characterized. All four receptors are G-protein coupled and activate inhibitory G proteins. These receptors form homo- and heterodimeric complexes and signal to kinase cascades and scaffold a variety of proteins.The authors discuss classic mechanisms and developments in understanding opioid tolerance and opioid receptor signaling and highlight advances in opioid molecular pharmacology, behavioral pharmacology, and human genetics. The authors put into context how opioid receptor signaling leads to the modulation of behavior with the potential for therapeutic intervention. Finally, the authors conclude there is a continued need for more translational work on opioid receptors in vivo.

Molecular mechanisms of opioid receptor-dependent signaling and behavior.

Mu opioid receptor (MOR) has been shown to be associated with alcoholism and opioid dependence The present study examined the involvement of a polymorphism in A118G in exon 1 and C1031G in intron 2 of the MOR gene in 200 Chinese heroin-dependent and 97 control subjects Results showed a significant association for both A118G and C1031G polymorphisms and opioid dependence The G allele is more common in the heroin-dependent group (395% and 308% for A118G and C1031G polymorphisms, respectively) when compared to the controls (294% and 211% for A118G and C1031G polymorphisms, respectively) This study suggests that the variant G allele of both A118G and C1031G polymorphisms may contribute to the vulnerability to heroin dependence

Association between mu opioid receptor gene polymorphisms and Chinese heroin addicts.

Dependent heroin use and associated risky behaviour: The role of rash impulsiveness and reward sensitivity

Methamphetamine (METH) is a monoaminergic toxin that destroys dopamine terminals and causes astrogliosis in vivo. Oxidative stress has been shown to play an important role in the toxic effects of METH. In the present study, we sought to determine whether astrocytes are involved in METH-induced oxidative stress. Reactive oxygen species (ROS), ATP, and change in mitochondria membrane potential (delta psi(m)) were examined in cultured striatal, mesencephalic, and cortical astrocytes after 4 to 48 h of 4 mM METH treatment. Results showed that only striatal and mesencephalic astrocytes showed a significant increase in ROS formation from 8 and 12 h, respectively. At 48 h treatment, there was a 55 and 53% increase in ROS content in striatal and mesencephalic astrocytes, respectively, whereas cortical astrocytes showed only a 25% (not significant) increase. JC-1, a delta psi(m)-sensitive dye, showed a decrease in delta psi(m) at 8 h treatment for striatal and mesencephalic astrocytes and at 12 h for cortical astrocytes. Astrocytes from all three regions showed a similar pattern of initial increase followed by a decrease in ATP content, with striatal astrocytes resulting in a maximum depletion (39% of control value) at 48 h treatment. These findings showed that METH treatment resulted in the formation of ROS in the order of striatal > mesencephalic > cortical astrocytes. Although the formation of ROS did not severely interfere with ATP production, a depolarization of mitochondria was observed. The present study suggested that astrocytes may be an important element governing the selective vulnerability to the striatum to METH-induced oxidative stress.

Alfreda Stadlin

Papers

Association between mu opioid receptor gene polymorphisms and Chinese heroin addicts.

Dependent heroin use and associated risky behaviour: The role of rash impulsiveness and reward sensitivity

Methamphetamine-induced oxidative stress in cultured mouse astrocytes.

Development of a postnatal 3-day-old rat model of mild hypoxic-ischemic brain injury.

Impulsivity in Hong Kong-Chinese club-drug users