The Role of the Aversive Effects of Drugs in Self-Administration: Assessing the Balance of Reward and Aversion in Drug-Taking Behavior.

The role of the aversive effects of drugs in self-administration: assessing the balance of reward and aversion in drug-taking behavior.

Behav Pharmacol. 2013 Jul 16;
Verendeev A, Riley AL

Since the first experimental demonstration that a drug of abuse supports instrumental behavior, drugs have been discussed in the context of their rewarding effects, which are assumed to drive and maintain drug-taking behavior. Indeed, drug reward has been fundamental in the formulation of most models of drug use, abuse, and addiction. Over the last several decades, however, drugs of abuse have been increasingly recognized as complex pharmacological compounds producing multiple stimulus effects, not all of which are rewarding. The aversive effects of such drugs, for example, have been described by a number of researchers working in the field, although few attempts have been made to investigate the role of these aversive effects in drug taking. The present paper offers a historical perspective on the view that drugs of abuse are complex pharmacological compounds with multiple stimulus effects. In doing so, we argue that the discussion of drug reward only may be insufficient in accounting for drug taking and we present evidence for the theoretical position that both the rewarding and the aversive effects of drugs should be taken into consideration in ongoing attempts to model drug-taking behavior. The present review summarizes several decades of research characterizing the aversive effects of major drugs of abuse, as well as more recent studies seeking to assess directly the role of drug aversion in drug taking. HubMed – addiction

Role of PI3K, mTOR and Akt2 signalling in hepatic tumorigenesis via the control of PKM2 expression.

Biochem Soc Trans. 2013 Aug 1; 41(4): 917-22
Nemazanyy I, Espeillac C, Pende M, Panasyuk G

To sustain increased growth, rapidly proliferating cells, such as tumour cells, undergo metabolic adaptations. In recent years, the mechanisms of glycolysis activation as a key metabolic adaptation in proliferating cells became the topic of intense research. Although this phenomenon was described more than 50 years ago by Otto Warburg, the molecular mechanisms remained elusive. Only recently, it was demonstrated that the expression of specific glycolytic enzymes, namely PKM2 (pyruvate kinase M2) and HK2 (hexokinase 2), occurs simultaneously with the glycolytic addiction of cancer cells. The PI3K (phosphoinositide 3-kinase)/mTOR [mammalian (or mechanistic) target of rapamycin] signalling pathway is a central signalling hub co-ordinating the growth in response to growth factor signalling and nutrient availability. Not surprisingly, it is found to be activated in the majority of the tumour cells. In the present article, we discuss the requirement of different PI3K/mTOR downstream effectors for the metabolic adaptation in liver cancer cells driven by this signalling pathway. We provide evidence for a selective involvement of the mTOR target Akt2 in tumoral growth. In addition, PTEN (phosphatase and tensin homologue deleted on chromosome 10)-negative human hepatocellular carcinoma cell lines display an up-regulation of PKM2 expression in an Akt2-dependent manner, providing an advantage for cell proliferation and anchorage-independent growth. Our data have implications on the link between the metabolic action of insulin signal transduction and tumorigenesis, identifying Akt2 as a potential therapeutical target in liver malignancies depending on cancer genotype. HubMed – addiction

Tobacco use among homeless people–addressing the neglected addiction.

N Engl J Med. 2013 Jul 18; 369(3): 201-4
Baggett TP, Tobey ML, Rigotti NA

HubMed – addiction

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