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Addictive Drugs (addictive + drug)

Distribution by Scientific Domains

Medical Sciences	46%
Life Sciences	46%

Selected Abstracts

ADDICTIVE DRUG USE MANAGEMENT POLICIES IN A LONG-RUN ECONOMIC MODEL,

AUSTRALIAN ECONOMIC PAPERS, Issue 2 2009
HARRY CLARKE
A model of illicit, addictive drug use is proposed when users have foresight. Impacts of drug use penalties, penalties on drug use-related crime, support for drug user rehabilitation as well as the effects of health-related, harm-minimisation policies are analysed. In the short run, government policies impact only on the drug use intensities of existing addicted and casual users. Longer term policy-induced user-cost changes impact on new user and addict numbers through their effect on recruitment into addiction and quit dynamics. Effects of policies on user numbers, usage intensities and impacts on long-run social costs are analysed over this long-term horizon. The model provides a setting for analysing the long-run effects of illicit drug management policies on the social costs of illicit drug use and allows assessment of drug use abstinence and harm minimisation policy tradeoffs. [source]

Ethanol-Induced Extracellular Signal Regulated Kinase: Role of Dopamine D1 Receptors

ALCOHOLISM, Issue 5 2009
Federico Ibba
Background:, Addictive drugs activate extracellular signal regulated kinase (ERK) in brain regions critically involved in their affective and motivational properties. The aim of this study was to demonstrate the ethanol-induced activation of ERK in the nucleus accumbens (Acb) and in the extended amygdala [bed nucleus of the stria terminalis lateralis (BSTL) and central nucleus of the amygdala (CeA)] and to highlight the role of dopamine (DA) D1 receptors in these effects. Methods:, Ethanol (0.5, 1, and 2 g/kg) was administered by gavage and ERK phosphorylation was determined in the nucleus Acb (shell and core), BSTL, and CeA by immunohistochemistry. The DA D1 receptor antagonist, SCH 39166 (SCH) (50 ,g/kg), was administered 10 minutes before ethanol (1 g/kg). Results:, Quantitative microscopic examination showed that ethanol, dose-dependently increased phospho-ERK immunoreactivity (optical and neuronal densities) in the shell and core of nucleus Acb, BSTL, and CeA. Pretreatment with SCH fully prevented the increases elicited by ethanol (1 g/kg) in all brain regions studied. Conclusions:, The results of this study indicate that ethanol, similar to other addictive drugs, activates ERK in nucleus Acb and extended amygdala via a DA D1 receptor-mediated mechanism. Overall, these results suggest that the D1 receptors/ERK pathway may play a critical role in the motivational properties of ethanol. [source]

PRECLINICAL STUDY: Proteomic analysis of methamphetamine-induced reinforcement processes within the mesolimbic dopamine system

ADDICTION BIOLOGY, Issue 3-4 2008
Moon Hee Yang
ABSTRACT Methamphetamine (MAP) is a commonly used, addictive drug, and a powerful stimulant that dramatically affects the central nervous system. In this study, we used the conditioned place preference (CPP) paradigm in order to study the reinforcing properties of MAP and the herewith associated changes in proteins within the mesolimbic dopamine system. A CPP was induced by MAP after three intermittent intraperitoneal injections (1 mg/kg) in rats and protein profiles in the nucleus accumbens, striatum, prefrontal cortex, cingulate cortex and hippocampus were compared with a saline-treated control group. In addition, a group of animals was run through extinction and protein profiles were compared with a non-extinguished group. Protein screening was conducted using two-dimensional electrophoresis analysis which identified 27 proteins in the group that showed MAP-induced CPP. Some of the proteins were confirmed by Western lot analysis. Identified proteins had functions related to the cytoskeleton, transport/endocytosis or exocytosis (e.g. profilin-2 and syntaxin-binding protein), and signal transduction, among others. [source]

Dissociation of food and opiate preference by a genetic mutation in zebrafish

GENES, BRAIN AND BEHAVIOR, Issue 7 2006
B. Lau
Both natural rewards and addictive substances have the ability to reinforce behaviors. It has been unclear whether identical neural pathways mediate the actions of both. In addition, little is known about these behaviors and the underlying neural mechanisms in a genetically tractable vertebrate, the zebrafish Danio rerio. Using a conditioned place preference paradigm, we demonstrate that wildtype zebrafish exhibit a robust preference for food as well as the opiate drug morphine that can be blocked by the opioid receptor antagonist naloxone. Moreover, we show that the too few mutant, which disrupts a conserved zinc finger-containing gene and exhibits a reduction of selective groups of dopaminergic and serotonergic neurons in the basal diencephalon, displays normal food preference but shows no preference for morphine. Pretreatment with dopamine receptor antagonists abolishes morphine preference in the wildtype. These studies demonstrate that zebrafish display measurable preference behavior for reward and show that the preference for natural reward and addictive drug is dissociable by a single-gene mutation that alters subregions of brain monoamine neurotransmitter systems. Future genetic analysis in zebrafish shall uncover further molecular and cellular mechanisms underlying the formation and function of neural circuitry that regulate opiate and food preference behavior. [source]

Role of endogenous acetylcholine in the control of the dopaminergic system via nicotinic receptors

JOURNAL OF NEUROCHEMISTRY, Issue 3 2010
Uwe Maskos
J. Neurochem. (2010) 114, 641,646. Abstract Nicotinic acetylcholine receptors (nAChRs) are pentameric membrane protein receptors activated by the addictive drug, nicotine. However, sometimes underestimated, under physiological conditions the endogenous neurotransmitter acetylcholine is the agonist. In this mini-review, I will discuss the evidence in favour of an important role for this cholinergic activation of the dopaminergic (DAergic) system. I will focus on the literature implicating the action of acetylcholine on the somato-dendritic compartment of these neurons. This modulation is responsible for a variety of phenotypes in knock-out animals of nAChR subunits. These include locomotion, exploratory behaviour, dopamine (DA) release, and DA neuron firing patterns. The novel techniques brought to bear on these analyses, lentiviral re-expression, and repression, of nAChR subunits, and transgenic expression of hypersensitive receptors will be discussed. [source]

Experience-dependent plasticity in hypocretin/orexin neurones: re-setting arousal threshold

ACTA PHYSIOLOGICA, Issue 3 2010
X.-B. Gao
Abstract The neuropeptide hypocretin is synthesized exclusively in the lateral hypothalamus and participates in many brain functions critical for animal survival, particularly in the promotion and maintenance of arousal in animals , a core process in animal behaviours. Consistent with its arousal-promoting role in animals, the neurones synthesizing hypocretin receive extensive innervations encoding physiological, psychological and environmental cues and send final outputs to key arousal-promoting brain areas. The activity in hypocretin neurones fluctuates and correlates with the behavioural state of animals and intensive activity has been detected in hypocretin neurones during wakefulness, foraging for food and craving for addictive drugs. Therefore, it is likely that hypocretin neurones undergo experience-dependent changes resulting from intensive activations by stimuli encoding changes in the internal and external environments. This review summarizes the most recent evidence supporting experience-dependent plasticity in hypocretin neurones. Current data suggest that nutritional and behavioural factors lead to synaptic plasticity and re-organization of synaptic architecture in hypocretin neurones. This may be the substrate of enhanced levels of arousal resulting from behavioural changes in animals and may help to explain the mechanisms underlying the changes in arousal levels induced by physiological, psychological and environmental factors. [source]

PRECLINICAL STUDY: FULL ARTICLE: Ethanol-induced activation of AKT and DARPP-32 in the mouse striatum mediated by opioid receptors

ADDICTION BIOLOGY, Issue 3 2010
Karl Björk
ABSTRACT The reinforcing properties of ethanol are in part attributed to interactions between opioid and dopaminergic signaling pathways, but intracellular mediators of such interactions are poorly understood. Here we report that an acute ethanol challenge induces a robust phosphorylation of two key signal transduction kinases, AKT and DARPP-32, in the striatum of mice. Ethanol-induced AKT phosphorylation was blocked by the opioid receptor antagonist naltrexone but unaffected by blockade of dopamine D2 receptors via sulpiride. In contrast, DARPP-32 phosphorylation was abolished by both antagonists. These data suggest that ethanol acts via two distinct but potentially synergistic striatal signaling cascades. One of these is D2-dependent, while the other is not. These findings illustrate that pharmacology of ethanol reward is likely more complex than that for other addictive drugs. [source]

Abnormal associative encoding in orbitofrontal neurons in cocaine-experienced rats during decision-making

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 9 2006
Thomas A. Stalnaker
Abstract Recent evidence has linked exposure to addictive drugs to an inability to employ information about adverse consequences, or outcomes, to control behavior. For instance, addicts and drug-experienced animals fail to adapt their behavior to avoid adverse outcomes in gambling and reversal tasks or after changes in the value of expected rewards. These deficits are similar to those caused by damage to the orbitofrontal cortex, suggesting that addictive drugs may cause long-lasting changes in the representation of outcome associations in a circuit that includes the orbitofrontal cortex. Here we test this hypothesis by recording from orbitofrontal neurons in a discrimination task in rats previously exposed to cocaine (30 mg/kg i.p. for 14 days). We found that orbitofrontal neurons recorded in cocaine-experienced rats failed to signal the adverse outcome at the time a decision was made in the task. The loss of this signal was associated with abnormal changes in response latencies on aversive trials. Furthermore, upon reversal of the cue,outcome associations, orbitofrontal neurons in cocaine-treated rats with enduring reversal impairments failed to reverse their cue-selectivity, while orbitofrontal neurons in cocaine-treated rats with normal performance showed an increase in the plasticity of cue-selective firing after reversal. These results provide direct neurophysiological evidence that exposure to cocaine can cause behaviorally relevant changes in the processing of associative information in a circuit that includes the orbitofrontal cortex. [source]

Insight Into the Relationship Between Impulsivity and Substance Abuse From Studies Using Animal Models

ALCOHOLISM, Issue 8 2010
Catharine A. Winstanley
Drug use disorders are often accompanied by deficits in the capacity to efficiently process reward-related information and to monitor, suppress, or override reward-controlled behavior when goals are in conflict with aversive or immediate outcomes. This emerging deficit in behavioral flexibility and impulse control may be a central component of the progression to addiction, as behavior becomes increasingly driven by drugs and drug-associated cues at the expense of more advantageous activities. Understanding how neural mechanisms implicated in impulse control are affected by addictive drugs may therefore prove a useful strategy in the search for new treatment options. Animal models of impulsivity and addiction could make a significant contribution to this endeavor. Here, some of the more common behavioral paradigms used to measure different aspects of impulsivity across species are outlined, and the importance of the response to reward-paired cues in such paradigms is discussed. Naturally occurring differences in forms of impulsivity have been found to be predictive of future drug self-administration, but drug exposure can also increase impulsive responding. Such data are in keeping with the suggestion that impulsivity may contribute to multiple stages within the spiral of addiction. From a neurobiological perspective, converging evidence from rat, monkey, and human studies suggest that compromised functioning within the orbitofrontal cortex may critically contribute to the cognitive sequelae of drug abuse. Changes in gene transcription and protein expression within this region may provide insight into the mechanism underlying drug-induced cortical hypofunction, reflecting new molecular targets for the treatment of uncontrolled drug-seeking and drug-taking behavior. [source]

Ethanol-Induced Extracellular Signal Regulated Kinase: Role of Dopamine D1 Receptors

Ethanol Attenuates the HFS-Induced, ERK-Mediated LTP in a Dose-Dependent Manner in Rat Striatum

ALCOHOLISM, Issue 1 2009
Gui Qin Xie
Background:, The striatum has been implicated to play a role in the control of voluntary behavior, and striatal synaptic plasticity is involved in instrumental learning. Ethanol is known to alter synaptic plasticity, in turn altering the behavior of human and animals. However, it remains unclear whether the striatum plays a role in the effects of ethanol on the central nervous system. The objective of this investigation was to study the effects of acute perfusion of ethanol on long-term potentiation (LTP) to elucidate the mechanisms of addictive drugs in the striatum. In addition, we investigated the contribution of intracellular extracellular signal regulated protein kinase (ERK) signaling pathway to corticostriatal LTP induction. Methods:, The stimulation evoked population spikes (PS) were recorded from the dorsomedial striatum (DMS) slices of rat using the extracellular recording technique. The LTP in DMS slices was induced by high-frequency stimulation (HFS). The ERK level of the DMS was assessed with the Western blot technique. Results:, U0126, the inhibitor of ERK, eliminated or significantly attenuated the LTP induced by HFS of the PS in the DMS. MK801 and APV, N -methyl- d -aspartic acid receptor (NMDAR) antagonists, inhibited the induction of striatal LTP, and HFS-induced ERK activation decreased in the slices treated with MK801 in the DMS. Clinically relevant concentrations of ethanol (22 to 88 mM) dose-dependently attenuated the HFS-induced striatal LTP and ERK activation in this brain region. Conclusions:, The LTP of the PS in the DMS is, at least partly, mediated by the ERK pathway coupling to NMDARs. Ethanol attenuated the HFS-induced, ERK-mediated LTP in a dose-dependent manner in this brain region. These results indicate that ethanol may change the synaptic plasticity of corticostriatal circuits underlying the learning of goal-directed instrumental actions, which is mediated by an intracellular ERK signaling pathway associated with NMDARs. [source]

The endocannabinoid system in brain reward processes

BRITISH JOURNAL OF PHARMACOLOGY, Issue 2 2008
M Solinas
Food, drugs and brain stimulation can serve as strong rewarding stimuli and are all believed to activate common brain circuits that evolved in mammals to favour fitness and survival. For decades, endogenous dopaminergic and opioid systems have been considered the most important systems in mediating brain reward processes. Recent evidence suggests that the endogenous cannabinoid (endocannabinoid) system also has an important role in signalling of rewarding events. First, CB1 receptors are found in brain areas involved in reward processes, such as the dopaminergic mesolimbic system. Second, activation of CB1 receptors by plant-derived, synthetic or endogenous CB1 receptor agonists stimulates dopaminergic neurotransmission, produces rewarding effects and increases rewarding effects of abused drugs and food. Third, pharmacological or genetic blockade of CB1 receptors prevents activation of dopaminergic neurotransmission by several addictive drugs and reduces rewarding effects of food and these drugs. Fourth, brain levels of the endocannabinoids anandamide and 2-arachidonoylglycerol are altered by activation of reward processes. However, the intrinsic activity of the endocannabinoid system does not appear to play a facilitatory role in brain stimulation reward and some evidence suggests it may even oppose it. The influence of the endocannabinoid system on brain reward processes may depend on the degree of activation of the different brain areas involved and might represent a mechanism for fine-tuning dopaminergic activity. Although involvement of the various components of the endocannabinoid system may differ depending on the type of rewarding event investigated, this system appears to play a major role in modulating reward processes. British Journal of Pharmacology (2008) 154, 369,383; doi:10.1038/bjp.2008.130; published online 14 April 2008 [source]

What neurobiology cannot tell us about addiction

ADDICTION, Issue 5 2010
Harold Kalant
ABSTRACT Molecular neurobiological studies have yielded enormous amounts of valuable information about neuronal response mechanisms and their adaptive changes. However, in relation to addiction this information is of limited value because almost every cell function appears to be involved. Thus it tells us only that neurons adapt to ,addictive drugs' as they do to all sorts of other functional disturbances. This information may be of limited help in the development of potential auxiliary agents for treatment of addiction. However, a reductionist approach which attempts to analyse addiction at ever finer levels of structure and function, is inherently incapable of explaining what causes these mechanisms to be brought into play in some cases and not in others, or by self-administration of a drug but not by passive exposure. There is abundant evidence that psychological, social, economic and specific situational factors play important roles in initiating addiction, in addition to genetic and other biological factors. Therefore, if we hope to be able to make predictions at any but a statistical level, or to develop effective means of prevention, it is necessary to devise appropriate integrative approaches to the study of addiction, rather than pursue an ever-finer reductive approach which leads steadily farther away from the complex interaction of drug, user, environment and specific situations that characterizes the problem in humans. [source]