A Review of Stress and Endogenous Opioid Interaction in Alcohol Addiction.

A review of stress and endogenous opioid interaction in alcohol addiction.

J Neurol Neurosurg Psychiatry. 2013 Sep; 84(9): e1
Emsley E, Lees R, Lingford-Hughes A, Nutt D

The endogenous opioid system (EOS) is involved in hedonic processing of reward, positive reinforcement, impulsivity, and potentially craving in alcohol dependence. Stress manifests in multiple stages of addiction, including early susceptibility to alcohol abuse, progression to dependence and risk of stress-related relapse. This literature review aims to collate evidence for the role of stress and opioid systems in alcohol addiction and identify novel interactions, with major importance in alcoholism treatment. Further, the actions of nalmefene and naltrexone, which may inform stress/opioid interaction in alcohol dependence, will be discussed.Published articles were identified with a MEDLINE search (January 1980 to March 2012). Key terms included: opioid, hypothalamic-pituitary-adrenal (HPA) axis, alcoholism, naltrexone, nalmefene. An initial review of titles preceded a second review of abstracts to identify articles meeting inclusion criteria.Alcohol addiction involves dysregulation of the EOS and stress systems, though precise abnormalities are uncertain. Normalisation of these systems in abstinence may occur, with inconsistent timings and degrees. The EOS has considerable interactions with stress at multiple levels of the HPA axis. Naltrexone, a relatively 1¼- specific opioid antagonist, paradoxically improves blunted 1(2)-endorphin activity in alcoholism. Naltrexone may also increase HPA responsiveness, with potential HPA normalisation, indicating an EOS-stress link. Nalmefene acts at all opioid receptors, especially K- which binds dynorphin. Dynorphin and stress interact in withdrawal, thus nalmefene may be effective in targeting relapse by negative reinforcement.Stress and EOS abnormalities in alcoholism, and extent of normalisation of these systems in abstinence, require further investigation. There is evidence for multifaceted interactions between opioid and stress systems in alcoholism. Since naltrexone and nalmefene have differential activity at EOS receptors, comprehensive characterisation of naltrexone and nalmefene action on stress systems is critical. Delineation of the effect of these drugs on HPA normalisation in abstinence, potentially via the EOS, is timely. This could ensure targeted and evidence-based care in those with alcohol dependency. HubMed – addiction

The Speed of Cocaine Delivery Determines the Subsequent Motivation to Self-Administer the Drug.

Neuropsychopharmacology. 2013 Jul 18;
Minogianis EA, Lévesque D, Samaha AN

The rapid delivery of drugs of abuse to the brain is associated with an increased likelihood and severity of addiction. Here we evaluated the hypothesis that rapidly delivered cocaine facilitates the addiction process by promoting the development of enhanced motivation for the drug. Rats lever-pressed for cocaine delivered intravenously over 5 or 90?s under fixed ratio (FR) during 6-h sessions. The motivation for cocaine was subsequently assessed using a progressive ratio (PR) schedule, where each successive drug injection cost an exponentially greater number of lever presses, until the cessation of responding. Throughout all self-administration sessions, all rats could only take one injection every 90?s. The 5-s groups self-administered more drug than the 90-s groups across the FR sessions. Under PR, animals that had chronically self-administered rapidly delivered cocaine took more cocaine across a range of doses and regardless of whether the drug was delivered over 5 or 90?s during PR testing. The speed of delivery also determined the long-term neurobiological impact of cocaine. Fourteen days following cocaine withdrawal, caudate-putamen D2 levels were decreased only in the 90-s rats, and quinpirole-mediated G?i/o-protein activation was increased to a greater extent in the 90- vs 5-s rats. Thus, rapid delivery promotes the pursuit of cocaine in the face of rising costs and alters cocaine-induced changes in striatal D2 receptor number and function. As such, rapidly delivered cocaine might facilitate addiction because it more readily alters brain motivation circuits in ways that contribute to the compulsive pursuit of the drug.Neuropsychopharmacology advance online publication, 7 August 2013; doi:10.1038/npp.2013.173. HubMed – addiction

Physiological Arousal Deficits in Addicted Gamers Differ Based on Preferred Game Genre.

Eur Addict Res. 2013 Aug 1; 20(1): 23-32
Metcalf O, Pammer K

Background/Aims: There has been significant discussion surrounding the psychopathology of excessive gaming and whether it constitutes an addiction. The current study investigated physiological and subjective levels of arousal in gamers of two genres and the relationship between sensation seeking and gaming addiction. Methods: Heart rate (HR), blood pressure (BP) and skin conductance were recorded at baseline, during gaming for 15 min and after gaming in 30 massively multiplayer online role-playing game (MMORPG) and 30 first-person shooter (FPS) male gamers. Gamers were identified as addicted using the Addiction-Engagement Questionnaire. Sensation seeking was measured using the Arnett Inventory of Sensation Seeking. Results: Addicted MMORPG gamers (n = 16) displayed significant decreases in cardiovascular activity during gaming compared to baseline and showed significant increases after gaming. Addicted FPS gamers (n = 13) had significant increases in BP during gaming which decreased significantly after gaming. In comparison, non-addicted MMORPG gamers (n = 14) had significant decreases in HR during gaming, whereas BP in non-addicted MMORPG and FPS gamers (n = 17) increased during gaming and after gaming. There were no significant relationships between sensation seeking and addiction. Conclusion: There are physiological arousal deficits in addicted gamers, and these patterns differ according to the genre of game played. HubMed – addiction