Cellular Signal Mechanisms of Reward-Related Plasticity in the Hippocampus.

Cellular signal mechanisms of reward-related plasticity in the hippocampus.

Filed under: Addiction Rehab

Neural Plast. 2012; 2012: 945373
Isokawa M

The hippocampus has the extraordinary capacity to process and store information. Consequently, there is an intense interest in the mechanisms that underline learning and memory. Synaptic plasticity has been hypothesized to be the neuronal substrate for learning. Ca(2+) and Ca(2+)-activated kinases control cellular processes of most forms of hippocampal synapse plasticity. In this paper, I aim to integrate our current understanding of Ca(2+)-mediated synaptic plasticity and metaplasticity in motivational and reward-related learning in the hippocampus. I will introduce two representative neuromodulators that are widely studied in reward-related learning (e.g., ghrelin and endocannabinoids) and show how they might contribute to hippocampal neuron activities and Ca(2+)-mediated signaling processes in synaptic plasticity. Additionally, I will discuss functional significance of these two systems and their signaling pathways for its relevance to maladaptive reward learning leading to addiction.
HubMed – addiction


Successful Smoking Cessation in COPD: Association with Comorbidities and Mortality.

Filed under: Addiction Rehab

Pulm Med. 2012; 2012: 725024
Kupiainen H, Kinnula VL, Lindqvist A, Postma DS, Boezen HM, Laitinen T, Kilpeläinen M

Smoking cessation is the cornerstone of COPD management, but difficult to achieve in clinical practice. The effect of comorbidities on smoking cessation and risk factors for mortality were studied in a cohort of 739 COPD patients recruited in two Finnish University Hospitals. The diagnosis of COPD was done for the first time on average 5.5 years prior to the enrollment. Data from the medical records and followup questionnaires (years 0, 1, 2, and 4) have been analyzed. The patients’ lung function varied greatly; mean FEV(1) 58% of predicted. A total of 60.2% of men and 55.6% of women had been able to quit smoking. Alcohol abuse (OR 2.1, 95% CI 1.4-3.3) and psychiatric conditions (OR 1.8, 95% CI 1.2-2.7) were strongly related to low success rates of quitting. Among current smokers high nicotine dependency was again explained by alcohol abuse and psychiatric conditions. Non-quitters were younger than quitters, but their mortality rates remained significantly higher even when the model was adjusted for impairment of lung functions and comorbidities. In conclusion, co-existing addiction and psychiatric diseases significantly decreased the success rates in smoking cessation and increased mortality among the patients.
HubMed – addiction


Designing opioids that deter abuse.

Filed under: Addiction Rehab

Pain Res Treat. 2012; 2012: 282981
Raffa RB, Pergolizzi JV, Muñiz E, Taylor R, Pergolizzi J

Prescription opioid formulations designed to resist or deter abuse are an important step in reducing opioid abuse. In creating these new formulations, the paradigm of drug development target should be introduced. Biological targets relating to the nature of addiction may pose insurmountable hurdles based on our current knowledge and technology, but products that use behavioral targets seem logical and feasible. The population of opioid abusers is large and diverse so behavioral targets are more challenging than they appear at first glance. Furthermore, we need to find ways to correlate behavioral observations of drug liking to actual use and abuse patterns. This may involve revisiting some pharmacodynamic concepts in light of drug effect rather than peak concentration. In this paper we present several new opioid analgesic agents designed to resist or deter abuse using physical barriers, the inclusion of an opioid agonist or antagonist, an aversive agent, and a prodrug formulation. Further, this paper also provides insight into the challenges facing drug discovery in this field. Designing and screening for opioids intended to resist or deter abuse is an important step to meet the public health challenge of burgeoning prescription opioid abuse.
HubMed – addiction


Genome wide expression profiling of the mesodiencephalic region identifies novel factors involved in early and late dopaminergic development.

Filed under: Addiction Rehab

Biol Open. 2012 Aug 15; 1(8): 693-704
Chakrabarty K, Von Oerthel L, Hellemons A, Clotman F, Espana A, Groot Koerkamp M, Holstege FC, Pasterkamp RJ, Smidt MP

Meso-diencephalic dopaminergic (mdDA) neurons are critical for motor control and cognitive functioning and their loss or dysfunction is associated with disorders such as Parkinson’s disease (PD), schizophrenia and addiction. However, relatively little is known about the molecular mechanisms underlying mdDA neuron development and maintenance. Here, we determined the spatiotemporal map of genes involved in the development of mdDA neurons to gain further insight into their molecular programming. Genome-wide gene expression profiles of the developing ventral mesencephalon (VM) were compared at different developmental stages leading to the identification of novel regulatory roles of neuronal signaling through nicotinic acthylcholine receptors (Chrna6 and Chrnb3 subunits) and the identification of novel transcription factors (Oc2 and 3) involved in the generation of the mdDA neuronal field. We show here that Pitx3, in cooperation with Nurr1, is the critical component in the activation of the Chrna6 and Chrnb3 subunits in mdDA neurons. Furthermore, we provide evidence of two divergent regulatory pathways resulting in the expression of Chrna6 and Chrnb3 respectively.
HubMed – addiction



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