Glucocorticoids Regulation of FosB/?FosB Expression Induced by Chronic Opiate Exposure in the Brain Stress System.
Glucocorticoids Regulation of FosB/?FosB Expression Induced by Chronic Opiate Exposure in the Brain Stress System.
Filed under: Addiction Rehab
PLoS One. 2012; 7(11): e50264
García-Pérez D, Laorden ML, Milanés MV, Núñez C
Chronic use of drugs of abuse profoundly alters stress-responsive system. Repeated exposure to morphine leads to accumulation of the transcription factor ?FosB, particularly in brain areas associated with reward and stress. The persistent effects of ?FosB on target genes may play an important role in the plasticity induced by drugs of abuse. Recent evidence suggests that stress-related hormones (e.g., glucocorticoids, GC) may induce adaptations in the brain stress system that is likely to involve alteration in gene expression and transcription factors. This study examined the role of GC in regulation of FosB/?FosB in both hypothalamic and extrahypothalamic brain stress systems during morphine dependence. For that, expression of FosB/?FosB was measured in control (sham-operated) and adrenalectomized (ADX) rats that were made opiate dependent after ten days of morphine treatment. In sham-operated rats, FosB/?FosB was induced after chronic morphine administration in all the brain stress areas investigated: nucleus accumbens(shell) (NAc), bed nucleus of the stria terminalis (BNST), central amygdala (CeA), hypothalamic paraventricular nucleus (PVN) and nucleus of the solitary tract noradrenergic cell group (NTS-A(2)). Adrenalectomy attenuated the increased production of FosB/?FosB observed after chronic morphine exposure in NAc, CeA, and NTS. Furthermore, ADX decreased expression of FosB/?FosB within CRH-positive neurons of the BNST, PVN and CeA. Similar results were obtained in NTS-A(2) TH-positive neurons and NAc pro-dynorphin-positive neurons. These data suggest that neuroadaptation (estimated as accumulation of FosB/?FosB) to opiates in brain areas associated with stress is modulated by GC, supporting the evidence of a link between brain stress hormones and addiction.
HubMed – addiction
Genetic deficiency in neprilysin or its pharmacological inhibition initiate excessive stress-induced alcohol consumption in mice.
Filed under: Addiction Rehab
PLoS One. 2012; 7(11): e50187
Maul B, Becker M, Gembardt F, Becker A, Schultheiss HP, Siems WE, Walther T
Both acquired and inherited genetic factors contribute to excessive alcohol consumption and the corresponding development of addiction. Here we show that the genetic deficiency in neprilysin [NEP] did not change the kinetics of alcohol degradation but led to an increase in alcohol intake in mice in a 2-bottle-free-choice paradigm after one single stress stimulus (intruder). A repetition of such stress led to an irreversible elevated alcohol consumption. This phenomenon could be also observed in wild-type mice receiving an orally active NEP inhibitor. We therefore elucidated the stress behavior in NEP-deficient mice. In an Elevated Plus Maze, NEP knockouts crossed more often the area between the arms, implicating a significant stronger stress response. Furthermore, such animals showed a decreased locomotor activity under intense light in a locomotor activity test, identifying such mice to be more responsive in aversive situations than their wild-type controls. Since the reduction in NEP activity itself does not lead to significant signs of an altered alcohol preference in mice but requires an environmental stimulus, our findings build a bridge between stress components and genetic factors in the development of alcoholism. Therefore, targeting NEP activity might be a very attractive approach for the treatment of alcohol abuse in a society with increasing social and financial stress.
HubMed – addiction
Hierarchical recruitment of phasic dopamine signaling in the striatum during the progression of cocaine use.
Filed under: Addiction Rehab
Proc Natl Acad Sci U S A. 2012 Nov 26;
Willuhn I, Burgeno LM, Everitt BJ, Phillips PE
Drug addiction is a neuropsychiatric disorder that marks the end stage of a progression beginning with recreational drug taking but culminating in habitual and compulsive drug use. This progression is considered to reflect transitions among multiple neural loci. Dopamine neurotransmission in the ventromedial striatum (VMS) is pivotal in the control of initial drug use, but emerging evidence indicates that once drug use is well established, its control is dominated by the dorsolateral striatum (DLS). In the current work, we conducted longitudinal neurochemical recordings to ascertain the spatiotemporal profile of striatal dopamine release and to investigate how it changes during the period from initial to established drug use. Dopamine release was detected using fast-scan cyclic voltammetry simultaneously in the VMS and DLS of rats bearing indwelling i.v. catheters over the course of 3 wk of cocaine self-administration. We found that phasic dopamine release in DLS emerged progressively during drug taking over the course of weeks, a period during which VMS dopamine signaling declined. This emergent dopamine signaling in the DLS mediated discriminated behavior to obtain drug but did not promote escalated or compulsive drug use. We also demonstrate that this recruitment of dopamine signaling in the DLS is dependent on antecedent activity in VMS circuitry. Thus, the current findings identify a striatal hierarchy that is instantiated during the expression of established responses to obtain cocaine.
HubMed – addiction
Characterization of a Novel alpha-Conotoxin from Conus textile that Selectively Targets Alpha6/alpha3beta2betab3 Nicotinic Acetylcholine Receptors.
Filed under: Addiction Rehab
J Biol Chem. 2012 Nov 26;
Luo S, Zhangsun D, Wu Y, Zhu X, Hu Y, McIntyre M, Christensen S, Akcan M, Craik DJ, McIntosh JM
Alpha6beta2 nicotinic acetylcholine receptors (nAChRs) expressed by dopaminergic neurons in the CNS are potential therapeutic targets for the treatment of several neuropsychiatric diseases, including nicotine addiction and Parkinson’s disease. However, recent studies indicate that the ?6 subunit can also associate with the ?4 subunit to form ?6?4 nAChRs that are difficult to pharmacologically distinguish from ?6?2, ?3?4 and ?3?2 subtypes. The current study characterized a novel 16 amino acid alpha-conotoxin (?-CTx) TxIB from Conus textile whose sequence is GCCSDPPCRNKHPDLC-amide as deduced from gene cloning. The peptide and an analog with an additional C-terminal glycine were chemically synthesized and tested on rat nAChRs heterologously expressed in Xenopus laevis oocytes. ?-CTx TxIB blocked ?6/?3?2?3 nAChR with an IC50 of 28 nM. In contrast, the peptide showed little or no block of other tested subtypes at concentrations up to 10 ?M. The three-dimensional solution structure of ?-CTx TxIB was determined using NMR spectroscopy. ?-CTx TxIB represents a uniquely selective ligand for probing the structure and function of ?6?2 nAChRs.
HubMed – addiction
Drug Addiction Treatment & Drug Rehab Help – Rehab–Centers.Net – Important information on drug addiction treatment and drug rehab programs. Find critical facts on addictions to Cocaine, Methadone, Heroin and Prescription Drugs. http
Find More Addiction Rehab Information…