Addiction Rehab: Selective Presynaptic Enhancement of the Prefrontal Cortex to Nucleus Accumbens Pathway by Cocaine.
Selective presynaptic enhancement of the prefrontal cortex to nucleus accumbens pathway by cocaine.
Filed under: Addiction Rehab
Proc Natl Acad Sci U S A. 2012 Dec 24;
Suska A, Lee BR, Huang YH, Dong Y, Schlüter OM
The nucleus accumbens (NAc) regulates motivated behavior by, in part, processing excitatory synaptic projections from several brain regions. Among these regions, the prefrontal cortex (PFC) and basolateral amygdala, convey executive control and affective states, respectively. Whereas glutamatergic synaptic transmission within the NAc has been recognized as a primary cellular target for cocaine and other drugs of abuse to induce addiction-related pathophysiological motivational states, the understanding has been thus far limited to drug-induced postsynaptic alterations. It remains elusive whether exposure to cocaine or other drugs of abuse influences presynaptic functions of these excitatory projections, and if so, in which projection pathways. Using optogenetic methods combined with biophysical assays, we demonstrate that the presynaptic release probability (Pr) of the PFC-to-NAc synapses was enhanced after short-term withdrawal (1 d) and long-term (45 d) withdrawal from either noncontingent (i.p. injection) or contingent (self-administration) exposure to cocaine. After long-term withdrawal of contingent drug exposure, the Pr was higher compared with i.p. injected rats. In contrast, within the basolateral amygdala afferents, presynaptic Pr was not significantly altered in any of these experimental conditions. Thus, cocaine-induced procedure- and pathway-specific presynaptic enhancement of excitatory synaptic transmission in the NAc. These results, together with previous findings of cocaine-induced postsynaptic enhancement, suggest an increased PFC-to-NAc shell glutamatergic synaptic transmission after withdrawal from exposure to cocaine. This presynaptic alteration may interact with other cocaine-induced cellular adaptations to shift the functional output of NAc neurons, contributing to the addictive emotional and motivational state.
HubMed – addiction
The ADH1B and DRD2 gene polymorphism may modify the protective effect of the ALDH2 gene against heroin dependence.
Filed under: Addiction Rehab
Prog Neuropsychopharmacol Biol Psychiatry. 2012 Dec 20;
Wang TY, Lee SY, Chen SL, Chang YH, Chen SH, Chu CH, Huang SY, Tzeng NS, Wang CL, Lee IH, Yeh TL, Yang YK, Lu RB
Understanding the influences of genes involved in dopamine and serotonin metabolism, such as the aldehyde dehydrogenase 2 (ALDH2) and alcohol dehydrogenase 1B (ADH1B) genes, is critical for understanding addictive behavior. In addition, dopamine D2 receptor (DRD2) gene may also interact with the dopamine metabolizing genes and link to addiction. Therefore, we investigated the association between the ALDH2, ADH1B and DRD2 polymorphisms and heroin dependence. Heroin-dependent Han Chinese patients (n=304) and healthy controls (n=335) were recruited. Genotypes of ALDH2, ADH1B and DRD2 polymorphisms were analyzed using a polymerase chain reaction with restriction fragment length polymorphism. The frequency of the ALDH2*1/*1 genotype was significantly lower in heroin-dependent patients than in controls, but the frequency of ADH1B and DRD2 genotypes was not significantly different. Further stratification of the ALDH2 gene with the ADH1B gene showed that the protective effect of ALDH2*1/*1 existed only in patients who also carried the ADH1B*1/*1 and ADH1B*1/*2 genotype. Logistic regression analysis showed a significant interaction between ALDH2 and ADH1B (P=0.022) and DRD2, ALDH2 and ADH1B in patients (P=0.037). The ALDH2*1/*1, ADH1B*1/*1, and ADH1B*1/*2 genotypes may interact and protect their carriers against heroin dependence and the protective effect may be varied by the DRD2 gene polymorphism. We conclude that the protective effect of the ALDH2 polymorphism against heroin dependence may be modified by the ADH1B and DRD2 polymorphism.
HubMed – addiction
Drink, drugs and disruption: memory manipulation for the treatment of addiction.
Filed under: Addiction Rehab
Curr Opin Neurobiol. 2012 Dec 21;
Milton A
Addiction is a complex disorder, and one characterised by the acquisition of maladaptive instrumental (drug-seeking and drug-taking) and pavlovian (cue-drug associations) memories. These memories markedly contribute to the long-term risk of relapse, so reduction of the impact of these memories on behaviour could potentially be an important addition to current therapies for addiction. Memory reconsolidation may provide such a target for disrupting well-consolidated pavlovian cue-drug memories following an extensive drug history. Reconsolidation can be disrupted either by administering amnestic drugs in conjunction with a memory reactivation session, or by updating the memory adaptively through the induction of ‘superextinction’. More work is needed before these therapies are ready for translation to the clinic, but if found clinically effective memory manipulation promises a radical new way of treating addiction.
HubMed – addiction
Psychiatric and medical comorbidities, associated pain, and health care utilization of patients prescribed buprenorphine.
Filed under: Addiction Rehab
J Subst Abuse Treat. 2012 Dec 19;
Mark TL, Dilonardo J, Vandivort R, Miller K
This study describes the comorbidities and health care utilization of individuals treated with buprenorphine using the 2007-2009 MarketScan Research Databases. Buprenorphine recipients had a high prevalence of comorbidities associated with chronic pain, including back problems (42%), connective tissue disease (24-27%), and nontraumatic joint disorders (20-23%). Approximately 69% of recipients filled prescriptions for opioid agonist medications in the 6months before buprenorphine initiation. Buprenorphine recipients were frequently diagnosed with anxiety (23-42%) and mood disorders (39-51%) and filled prescriptions for antidepressants (47-56%) and benzodiazepines (47-56%) at high rates. Surprisingly, only 53-54% of patients filling a prescription for buprenorphine had a coded opioid abuse/dependence diagnosis. Research is needed to better understand buprenorphine’s effectiveness in the context of prescription drug abuse and the best way to coordinate services to address the patient’s comorbid addiction, pain, and psychiatric illnesses.
HubMed – addiction
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