The ?-Opioid Receptor and Treatment Response to Naltrexone.

The ?-Opioid Receptor and Treatment Response to Naltrexone.

Alcohol Alcohol. 2013 Mar 29;
Thorsell A

AIMS: To evaluate the pharmacogenetic evidence relating to the use of opioid antagonists (in particular naltrexone) in treating patients with alcohol abuse problems. METHODS: Narrative review of pre-clinical and clinical published research regarding genetic modulation of psychotropic effects produced by alcohol and the therapeutic effects of opioid antagonists. RESULTS: Alcohol activates brain reward pathways, leading to positive reinforcement of alcohol seeking and consumption. Thus, the underlying biological mechanisms may be targets for treatment, particularly in the early stages of addiction development. Alcohol reward is in part mediated by endogenous opioids. A single-nucleotide polymorphism (SNP) within the OPRM1 gene, A118G, leading to an amino acid change (Asn40Asp) in the extracellular portion of the receptor, has been implicated in alcoholism as well as in drug addiction, pain sensitivity and stress response, and in animal and human studies relates to the alcohol-dependent phenotype as well as to the treatment response to the µ-opioid antagonist naltrexone. CONCLUSION: The effect size reported in naltrexone clinical studies is often small, which may be due to heterogeneity among patients. Pharmacogenetic approaches may help guide us in the search for the appropriate treatment optimal for one patient’s need. HubMed – addiction


The Role of GABAB Receptors in Morphine Self-Administration.

Int J Prev Med. 2013 Feb; 4(2): 158-64
Ramshini E, Alaei H, Reisi P, Alaei S, Shahidani S

There is only little information about the effects of GABA receptors agonist and antagonist on morphine self-administration. Present study was designed to assess role of GABAB receptors in the regulation of morphine-reinforced self-administration.THIS STUDY WAS PERFORMED IN FOUR GROUPS OF RATS: (1) Saline group, which received saline in the self-administration session. (2) Morphine group, which received morphine in saline solution in the self-administration session. (3) Baclofen + Morphine group, which received both baclofen 20 min before self- administration test and morphine in the self-administration session. (4) Phaclofen + Morphine group, which received both phaclofen 20 min before self- administration test and morphine in the self-administration session. The number of lever pressing and self-infusion were recorded.Morphine significantly increased the number of active lever pressing dose dependently in self-administration session in comparative with saline group. Administration of baclofen, 20 min before morphine self-administration produced significant decrease in the initiation of morphine self-administration during all session. Conversely, pre-treatment of phaclofen increased the number of active lever pressing and self-infusion in this test.Our results indicated a short-term treatment by baclofen, reduced morphine-maintenance response in a dose-dependent manner, suggesting that GABAB receptor agonists could be useful for reversing the neuroadaptations related to opiates. HubMed – addiction


Strengthening the accumbal indirect pathway promotes resilience to compulsive cocaine use.

Nat Neurosci. 2013 Mar 31;
Bock R, Shin JH, Kaplan AR, Dobi A, Markey E, Kramer PF, Gremel CM, Christensen CH, Adrover MF, Alvarez VA

A hallmark of addiction is the loss of control over drug intake, which is seen in only a fraction of those exposed to stimulant drugs such as cocaine. The cellular mechanisms underlying vulnerability or resistance to compulsive drug use remain unknown. We found that individual variability in the development of highly motivated and perseverative behavior toward cocaine is associated with synaptic plasticity in medium spiny neurons expressing dopamine D2 receptors (D2-MSNs) in the nucleus accumbens (NAc) of mice. Potentiation of glutamatergic inputs onto indirect pathway D2-MSNs was associated with resilience toward compulsive cocaine seeking. Inhibition of D2-MSNs using a chemicogenetic approach enhanced the motivation to obtain cocaine, whereas optogenetic activation of D2-MSNs suppressed cocaine self-administration. These results indicate that recruitment of D2-MSNs in NAc functions to restrain cocaine self-administration and serves as a natural protective mechanism in drug-exposed individuals. HubMed – addiction


Serum carbohydrate deficient transferrin as a sensitive marker in diagnosing alcohol abuse: a case – control study.

J Clin Diagn Res. 2013 Feb; 7(2): 197-200
Madhubala V, Subhashree AR, Shanthi B

Background: Alcoholism is a major problem in India thereby causing a heavy toll on the health related expenditure of the country. Detection of alcohol abuse rely mainly on clinical details which is sometimes inaccurate or unreliable and hence using a specific diagnostic parameter might be of immense use not only for early diagnosis but also during follow up of the cases. Aims and Objectives: This case control study aimed at evaluating the usefulness of Carbohydrate Deficient Transferrin (CDT) as a sensitive marker to diagnose alcohol abuse. Materials and Methods: The study was approved by Institutional research and ethical committee. Twenty five known male alcoholics who attended to the OPD (Out Patient Department) of Alcohol de-addiction centre of a tertiary care hospital were selected as cases. All of them were diagnosed to have a strong likely hood of hazardous alcohol consumption based on ‘Alcohol Use Disorders Identification Test” (AUDIT) questionnaire. Twenty five age matched, gender matched healthy individuals who were teetotalers were selected as controls. They scored zero in AUDIT questionnaire. Informed consent was obtained from all the cases and controls. The following tests were done: Liver function tests including Serum Bilirubin, Total Proteins, Aspartate Amino Transferase (AST), Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Gamma Glutamyl Transferase (GGT) and Blood glucose levels were estimated using a fully automated biochemistry analyser, XL – 300 (Trans Asia Biomedical systems) and Mean Corpuscular Volume (MCV) was done using an automated hematology analyser Sysmex KX-21. Percentage of Serum Carbohydrate Deficient Transferrin (%CDT) was assessed using immuno Turbidimetric assay, ELISA method (iMark, Bio-Rad Laboratories,). Statistical analysis of the data obtained was done using SPSS 16.0. Results: There was a statistically significant difference in values of AST, ALT, ALP, MCV, GGT and % CDT in cases as compared to controls. ROC curves drawn to assess the sensitivity and specificity of each parameter showed that %CDT has the highest sensitivity and specificity (84% and 92% respectively) and MCV (48% and 52% respectively) had the least. GGT when compared to % CDT had a lower sensitivity and specificity (64% and 72% respectively). Conclusion: % CDT is a sensitive biomarker which can be used to diagnose alcohol abuse and is superior to GGT in terms of sensitivity as well as specificity. HubMed – addiction



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