Regulation of the extrinsic and intrinsic apoptotic pathways in the prefrontal cortex of short- and long-term human opiate abusers

  title={Regulation of the extrinsic and intrinsic apoptotic pathways in the prefrontal cortex of short- and long-term human opiate abusers},
  author={M. Julia Garc{\'i}a-Fuster and Alfredo Ramos-Miguel and Guadalupe Rivero and Romano La Harpe and J. Javier Meana and Jes{\'u}s A Garc{\'i}a-Sevilla},

Role of Multifunctional FADD (Fas-Associated Death Domain) Adaptor in Drug Addiction

Brain neuroadaptations along the reward system are a focus of current research, especially those induced in the prefrontal cortex of human addicts, and appear to be major causes for compulsive drug-seeking behavior despite the negative effects of drugs of abuse.

Correlation of rat cortical Fas-associated death domain (FADD) protein phosphorylation with the severity of spontaneous morphine abstinence syndrome: role of α2-adrenoceptors and extracellular signal-regulated kinases

Data indicate that cortical oligomeric p-FADD, mainly through an interaction with inhibitory α2-adrenoceptors, plays a functional role in the behavioural expression of morphine abstinence in rats.



Modulation of Fas receptor proteins and dynamin during opiate addiction and induction of opiate withdrawal in rat brain

The main results indicate that chronic heroin/morphine treatment and heroin withdrawal are associated with up-regulation of 35 kDa native Fas (and with different expressions of glycosylated Fas), and also with concomitant increases of dynamin in rat brain.

Chronic methadone treatment and repeated withdrawal impair cognition and increase the expression of apoptosis-related proteins in mouse brain

The data suggest that neural apoptotic damage could contribute to impairment of the cognitive abilities of mice observed after chronic methadone administration and withdrawal, and indicates that tolerance to most of the deleterious effects develops after chronic administration.

Effect of Cocaine on Fas-Associated Protein with Death Domain in the Rat Brain: Individual Differences in a Model of Differential Vulnerability to Drug Abuse

FADD is a signaling protein modulated by cocaine, regulating apoptosis/proliferative mechanisms in relation to its FADD/pFADD content, suggesting FADD may also be a molecular correlate for the HR/LR phenotype.

Effects of Opiate Drugs on Fas-Associated Protein with Death Domain (FADD) and Effector Caspases in the Rat Brain: Regulation by the ERK1/2 MAP Kinase Pathway

The results indicate that μ- and δ-opioid receptors have a prominent role in the modulation of FADD (opposite to that of Fas) shortly after initiating treatment, which in turn is dependent on the activation of the antiapoptotic ERK1/2 signaling pathway.

Modulation of apoptosis in the mouse brain after morphine treatments and morphine withdrawal

A neurotoxic effect exerted by chronic, but not acute, morphine and its withdrawal is suggested by activating both the intrinsic and the extrinsic apoptotic pathways.

Opioids As Modulators of Cell Death and Survival—Unraveling Mechanisms and Revealing New Indications

The present review tries to unravel controversial findings and provides a hypothesis that may help to integrate diverse results that are still unclear whether these properties are mediated through typical opioid receptor activation and inhibitory G-protein-signaling.

Neuronal Apoptosis Associated with Morphine Tolerance: Evidence for an Opioid-Induced Neurotoxic Mechanism

It is demonstrated that spinal neuronal apoptosis was induced in rats made tolerant to morphine administered through intrathecal boluses or continuous infusion, indicating an opioid-induced neurotoxic consequence regulated by the NMDAR–caspase pathway, a mechanism that may have clinical implications in opioid therapy and substance abuse.

Alteration of caspases and apoptosis-related proteins in brains of patients with Alzheimer's disease.

The current findings showed that dysregulation of apoptotic proteins indeed exists in AD brain and support the notion that it may contribute to neuropathology of AD, and further hints that apoptosis in AD may occur via the death receptor pathway independent of cytochrome c.

Drug Addiction as a Pathology of Staged Neuroplasticity

The neuroplasticity in brain circuits and cell function induced by addictive drugs that is thought to underlie the compulsions to resume drug-taking is described and discussed, and how this knowledge is impelling exploration and testing of novel addiction therapies.

Chronic morphine induces up‐regulation of the pro‐apoptotic Fas receptor and down‐regulation of the anti‐apoptotic Bcl‐2 oncoprotein in rat brain

It is indicated that morphine, through the sustained activation of opioid receptors, can promote abnormal programmed cell death by enhancing the expression of pro‐apoptotic Fas receptor protein and damping theexpression of anti‐ap optotic Bcl‐2 oncoprotein.