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.

GABAA receptor subunit genes clustered on 5q33 play a role in the development of alcoholism and methamphetamine use disorder without psychosis. The present study explored the possible contribution of the same subunit genes to the development of heroin dependence. Single nucleotide polymorphisms (SNPs) of the GABAA receptor subunits GABRB2, GABRA6, GABRA1, and GABRG2 were examined in 178 male Han Chinese heroin-dependent and 170 male control subjects. A significant difference in allele frequency for the SNP rs211014 in the GABAAγ2 receptor subunit gene between cases and controls was identified (P = 0.015). A possible mechanism for the involvement of the GABA receptor subunit genes on 5q33 in the development of heroin dependence is discussed. © 2007 Wiley-Liss, Inc.

Association analysis of GABA receptor subunit genes on 5q33 with heroin dependence in a Chinese male population.

Effects of tumor necrosis factor alpha on taurine uptake in cultured rat astrocytes.

Postnatal changes in [3H]mazindol-labelled dopamine uptake sites in the rat striatum following prenatal cocaine exposure.

Induction of tumor necrosis factor receptor type 2 gene expression by tumor necrosis factor-α in rat primary astrocytes

Heroin users exhibit abnormal pain sensitivity called opioid-induced hyperalgesia that may weaken their determination to abstain. The dopamine receptor D4 gene (DRD4) is associated with heroin dependence; one of its polymorphisms is a C/T variation 521 bp upstream to the gene (−521C/T). We investigated whether this polymorphism was related to opioid dependence through modulation of cold-pain responses. We recruited 84 heroin-dependent Chinese male subjects and 168 healthy male Chinese controls. Genotyping was performed by PCR-RFLP. A significantly higher T allele frequency was observed in the heroin group (P= 0.041). Of the cohort recruited, 43 current heroin users and 66 controls were further subjected to a cold-pressor test (CPT) to determine their pain threshold and tolerance. TT controls demonstrated a significantly lower pain threshold than did their CC/CT counterparts (P= 0.022) and TT opioid users (P= 0.006). Moreover, CC/CT controls had a significantly higher pain tolerance than TT controls (P= 0.042) and CC/CT opioid users (P= 0.010). The data suggest that DRD4−521C/T plays an important role in opioid dependence through modulating cold-pain responses. TT individuals might have a higher tendency to use opioids because they experience pain less strongly after chronic opioid use. © 2009 The New York Academy of Sciences.

Alfreda Stadlin

Papers

Association analysis of GABA receptor subunit genes on 5q33 with heroin dependence in a Chinese male population.

Effects of tumor necrosis factor alpha on taurine uptake in cultured rat astrocytes.

Postnatal changes in [3H]mazindol-labelled dopamine uptake sites in the rat striatum following prenatal cocaine exposure.

Induction of tumor necrosis factor receptor type 2 gene expression by tumor necrosis factor-α in rat primary astrocytes

Dopamine Receptor D4 Gene −521C/T Polymorphism Is Associated with Opioid Dependence through Cold-Pain Responses