Morphine Withdrawal Enhances Constitutive ?-Opioid Receptor Activity in the Ventral Tegmental Area.

Morphine Withdrawal Enhances Constitutive ?-Opioid Receptor Activity in the Ventral Tegmental Area.

Filed under: Addiction Rehab

J Neurosci. 2012 Nov 14; 32(46): 16120-16128
Meye FJ, van Zessen R, Smidt MP, Adan RA, Ramakers GM

?-Opioid receptors (MORs) in the ventral tegmental area (VTA) are pivotally involved in addictive behavior. While MORs are typically activated by opioids, they can also become constitutively active in the absence of any agonist. In the current study, we present evidence that MOR constitutive activity is highly relevant in the mouse VTA, as it regulates GABAergic input to dopamine neurons. Specifically, suppression of MOR constitutive activity with the inverse agonist KC-2-009 enhanced GABAergic neurotransmission onto VTA dopamine neurons. This inverse agonistic effect was fully blocked by the specific MOR neutral antagonist CTOP, which had no effect on GABAergic transmission itself. We next show that withdrawal from chronic morphine further increases the magnitude of inverse agonistic effects at the MOR, suggesting enhanced MOR constitutive activity. We demonstrate that this increase can be an adaptive response to the detrimental elevation in cAMP levels known to occur during morphine withdrawal. These findings offer important insights in the physiological occurrence and function of MOR constitutive activity, and have important implications for therapeutic strategies aimed at normalizing MOR signaling during addiction and opioid overdose.
HubMed – addiction

 

Dynorphin – Still an Extraordinarily Potent Opioid Peptide.

Filed under: Addiction Rehab

Mol Pharmacol. 2012 Nov 14;
Chavkin C

This issue of Molecular Pharmacology is dedicated to Dr. Avram Goldstein, the journal’s founding Editor and one of the leaders in the development of modern pharmacology. This chapter focuses on his contributions to the discovery of the dynorphins and evidence that members of this family of opioid peptides are endogenous agonists for the kappa opioid receptor. In his original publication describing the purification and sequencing of dynorphin A, Avram described this peptide as ‘extraordinarily potent’ (‘dyn’ from the Greek, dynamis = power and ‘-orphin’ for endogenous morphine peptide). The name originally referred to its high affinity and great potency in the bioassay that was used to follow its activity during purification, but the name has come to have a second meaning: Studies of its physiological function in brain continue to provide powerful insights to the molecular mechanisms controlling the mood disorders and drug addiction. In the 30 years since its discovery, we have learned that the dynorphin peptides are released in brain during stress exposure. Once released, they activate kappa opioid receptors distributed throughout the brain and spinal cord where they trigger cellular responses resulting in different stress responses: analgesia, dysphoria-like behaviors, anxiety-like responses, and increased addiction behaviors in experimental animals. Avram predicted that a detailed molecular analysis of opiate drug actions would someday lead to better treatments for drug addiction, and he would be gratified to know that subsequent studies enabled by his discovery of the dynorphins resulted in insights that hold great promise for new treatments for addiction and depressive disorders.
HubMed – addiction

 

Maternal cocaine use during breastfeeding.

Filed under: Addiction Rehab

Can Fam Physician. 2012 Nov; 58(11): 1218-1219
Cressman AM, Koren G, Pupco A, Kim E, Ito S, Bozzo P

Question In my practice several patients have struggled with cocaine abuse during their pregnancies. One woman, now postpartum, wants to breastfeed her infant. Despite being abstinent for the final few months of her pregnancy, I am concerned about the potential adverse effects on her child if she happens to relapse. What is the current evidence about the risks of cocaine exposure during breastfeeding? Answer Given the substantial benefits of breastfeeding for infant health and development, there is no reason for mothers who previously abused cocaine to avoid breastfeeding. It is important for the health care team to counsel patients both on the serious potential risks of cocaine exposure for babies and on the benefits of breastfeeding, to allow for an informed choice. Additionally, attempts should be made to estimate maternal commitment to breastfeeding and discontinuation of cocaine use, and to offer addiction counseling to mitigate the potential risks of infant cocaine exposure. It is paramount to minimize the risk to the infant, which would certainly include mothers ceasing use of cocaine while breastfeeding. For mothers who elect to breastfeed and use cocaine intermittently, breastfeeding should be delayed sufficiently after cocaine use to allow for drug elimination (approximately 24 hours).
HubMed – addiction

 

Psychosocial interventions to reduce alcohol consumption in concurrent problem alcohol and illicit drug users.

Filed under: Addiction Rehab

Cochrane Database Syst Rev. 2012; 11: CD009269
Klimas J, Field CA, Cullen W, O’Gorman CS, Glynn LG, Keenan E, Saunders J, Bury G, Dunne C

BACKGROUND: Problem alcohol use is common among illicit drug users and is associated with adverse health outcomes. It is also an important factor in poor prognosis among drug users with hepatitis C virus (HCV) as it impacts on progression to hepatic cirrhosis or opiate overdose in opioid users. OBJECTIVES: To assess the effects of psychosocial interventions for problem alcohol use in illicit drug users (principally problem drug users of opiates and stimulants). SEARCH METHODS: We searched the Cochrane Drugs and Alcohol Group trials register (November 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 11, November 2011), PUBMED (1966 to 2011); EMBASE (1974 to 2011); CINAHL (1982 to 2011); PsycINFO (1872 to 2011) and reference list of articles. We also searched: 1) conference proceedings (online archives only) of the Society for the Study of Addiction (SSA), International Harm Reduction Association (IHRA), International Conference on Alcohol Harm Reduction (ICAHR), and American Association for the Treatment of Opioid Dependence (AATOD); 2) online registers of clinical trials, Current Controlled Trials (CCT), Clinical Trials.org, Center Watch and International Clinical Trials Registry Platform (ICTRP). SELECTION CRITERIA: Randomised controlled trials comparing psychosocial interventions with another therapy (other psychosocial treatment, including non-pharmacological therapies or placebo) in adult (over the age of 18 years) illicit drug users with concurrent problem alcohol use. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed risk of bias and extracted data from included trials. MAIN RESULTS: Four studies, 594 participants, were included. Half of the trials were rated as having high or unclear risk of bias. They considered six different psychosocial interventions grouped into four comparisons: (1) cognitive-behavioural coping skills training versus 12-step facilitation (N = 41), (2) brief intervention versus treatment as usual (N = 110), (3) hepatitis health promotion versus motivational interviewing (N = 256), and (4) brief motivational intervention versus assessment-only group (N = 187). Differences between studies precluded any pooling of data. Findings are described for each trial individually:comparison 1: no significant difference; comparison 2: higher rates of decreased alcohol use at three months (risk ratio (RR) 0.32; 95% confidence interval (CI) 0.19 to 0.54) and nine months (RR 0.16; 95% CI 0.08 to 0.33) in the treatment as usual group; comparison 3 (group and individual format): no significant difference; comparison 4: more people reduced alcohol use (by seven or more days in the past 30 days at 6 months) in the brief motivational intervention compared to controls (RR 1.67; 95% CI 1.08 to 2.60). AUTHORS’ CONCLUSIONS: Very little evidence exists that there is no difference in the effectiveness between different types of interventions and that brief interventions are not superior to assessment only or treatment as usual. No conclusion can be made because of the paucity of the data and the low quality of the retrieved studies.
HubMed – addiction

 


 

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