共查询到20条相似文献，搜索用时 31 毫秒
1.
Both impulsivity and novelty-seeking have been suggested to be behavioral markers of the propensity to take addictive drugs. However, their relevance for the vulnerability to compulsively seek and take drugs, which is a hallmark feature of addiction, is unknown. We report here that, whereas high reactivity to novelty predicts the propensity to initiate cocaine self-administration, high impulsivity predicts the development of addiction-like behavior in rats, including persistent or compulsive drug-taking in the face of aversive outcomes. This study shows experimental evidence that a shift from impulsivity to compulsivity occurs during the development of addictive behavior, which provides insights into the genesis and neural mechanisms of drug addiction. 相似文献
2.
Treatment efforts for cocaine addiction are hampered by high relapse rates. To map brain areas underlying relapse, we used electrical brain stimulation and intracranial injection of pharmacological compounds after extinction of cocaine self-administration behavior in rats. Electrical stimulation of the hippocampus containing glutamatergic fibers, but not the medial forebrain bundle containing dopaminergic fibers, elicited cocaine-seeking behavior dependent on glutamate in the ventral tegmental area. This suggests a role for glutamatergic neurotransmission in relapse to cocaine abuse. The medial forebrain bundle electrodes supported intense electrical self-stimulation. These findings suggest a dissociation of neural systems subserving positive reinforcement (self-stimulation) and incentive motivation (relapse). 相似文献
3.
Compulsive drug use in the face of adverse consequences is a hallmark feature of addiction, yet there is little preclinical evidence demonstrating the actual progression from casual to compulsive drug use. Presentation of an aversive conditioned stimulus suppressed drug seeking in rats with limited cocaine self-administration experience, but no longer did so after an extended cocaine-taking history. In contrast, after equivalent extended sucrose experience, sucrose seeking was still suppressed by an aversive conditioned stimulus. Persistent cocaine seeking in the presence of signals of environmental adversity after a prolonged cocaine-taking history was not due to impaired fear conditioning, nor to an increase in the incentive value of cocaine, and may reflect the establishment of compulsive behavior. 相似文献
4.
Cocaine abuse has reached epidemic proportions in the United States, and the search for an effective pharmacotherapy continues. Because primates self-administer most of the drugs abused by humans, they can be used to predict the abuse liability of new drugs and for preclinical evaluation of new pharmacotherapies for drug abuse treatment. Daily administration of buprenorphine (an opioid mixed agonist-antagonist) significantly suppressed cocaine self-administration by rhesus monkeys for 30 consecutive days. The effects of buprenorphine were dose-dependent. The suppression of cocaine self-administration by buprenorphine did not reflect a generalized suppression of behavior. These data suggest that buprenorphine would be a useful pharmacotherapy for treatment of cocaine abuse. Because buprenorphine is a safe and effective pharmacotherapy for heroin dependence, buprenorphine treatment may also attenuate dual abuse of cocaine and heroin. 相似文献
5.
Dalley JW Fryer TD Brichard L Robinson ES Theobald DE Lääne K Peña Y Murphy ER Shah Y Probst K Abakumova I Aigbirhio FI Richards HK Hong Y Baron JC Everitt BJ Robbins TW 《Science (New York, N.Y.)》2007,315(5816):1267-1270
Stimulant addiction is often linked to excessive risk taking, sensation seeking, and impulsivity, but in ways that are poorly understood. We report here that a form of impulsivity in rats predicts high rates of intravenous cocaine self-administration and is associated with changes in dopamine (DA) function before drug exposure. Using positron emission tomography, we demonstrated that D2/3 receptor availability is significantly reduced in the nucleus accumbens of impulsive rats that were never exposed to cocaine and that such effects are independent of DA release. These data demonstrate that trait impulsivity predicts cocaine reinforcement and that D2 receptor dysfunction in abstinent cocaine addicts may, in part, be determined by premorbid influences. 相似文献
6.
Clinical observations show that there is considerable individual variability in the response to the addictive properties of drugs. This individual variability needs to be taken into account in animal models of addiction. Like humans, only some rats readily self-administer low doses of psychostimulants. The individual animals at risk can be identified on the basis of their response to environmental or pharmacological challenges. This predisposition to develop self-administration can be induced by repeated treatment with amphetamine. These results may help elucidate the neurobiological basis of addiction liability observed in both rats and humans. 相似文献
7.
A number of brain systems have been implicated in addictive behavior, but none have yet been shown to be necessary for maintaining the addiction to cigarette smoking. We found that smokers with brain damage involving the insula, a region implicated in conscious urges, were more likely than smokers with brain damage not involving the insula to undergo a disruption of smoking addiction, characterized by the ability to quit smoking easily, immediately, without relapse, and without persistence of the urge to smoke. This result suggests that the insula is a critical neural substrate in the addiction to smoking. 相似文献
8.
Witten IB Lin SC Brodsky M Prakash R Diester I Anikeeva P Gradinaru V Ramakrishnan C Deisseroth K 《Science (New York, N.Y.)》2010,330(6011):1677-1681
Cholinergic neurons are widespread, and pharmacological modulation of acetylcholine receptors affects numerous brain processes, but such modulation entails side effects due to limitations in specificity for receptor type and target cell. As a result, causal roles of cholinergic neurons in circuits have been unclear. We integrated optogenetics, freely moving mammalian behavior, in vivo electrophysiology, and slice physiology to probe the cholinergic interneurons of the nucleus accumbens by direct excitation or inhibition. Despite representing less than 1% of local neurons, these cholinergic cells have dominant control roles, exerting powerful modulation of circuit activity. Furthermore, these neurons could be activated by cocaine, and silencing this drug-induced activity during cocaine exposure (despite the fact that the manipulation of the cholinergic interneurons was not aversive by itself) blocked cocaine conditioning in freely moving mammals. 相似文献
9.
The success of forward genetic (from phenotype to gene) approaches to uncover genes that drive the molecular mechanism of circadian clocks and control circadian behavior has been unprecedented. Links among genes, cells, neural circuits, and circadian behavior have been uncovered in the Drosophila and mammalian systems, demonstrating the feasibility of finding single genes that have major effects on behavior. Why was this approach so successful in the elucidation of circadian rhythms? This article explores the answers to this question and describes how the methods used successfully for identifying the molecular basis of circadian rhythms can be applied to other behaviors such as anxiety, addiction, and learning and memory. 相似文献
10.
Fenfluramine: amphetamine congener that fails to maintain drug-taking behavior in the rhesus monkey 总被引：1，自引：0，他引：1
Fenfluramine, over a dose range from 0.003 to 3 milligrams per kilogram of body weight, failed to maintain self-injection behavior in rhesus monkeys that had initiated and maintained responding for cocaine or methohexital. This absence of a positive reinforcing effect could not be attributed to a slow onset of drug effect or to the use of behaviorally inactive doses. Fenfluramine, because of its distinctive properties, may produce fewer problems of human abuse than do amphetamine-type agents. 相似文献
11.
Ersche KD Jones PS Williams GB Turton AJ Robbins TW Bullmore ET 《Science (New York, N.Y.)》2012,335(6068):601-604
Addiction to drugs is a major contemporary public health issue, characterized by maladaptive behavior to obtain and consume an increasing amount of drugs at the expense of the individual's health and social and personal life. We discovered abnormalities in fronto-striatal brain systems implicated in self-control in both stimulant-dependent individuals and their biological siblings who have no history of chronic drug abuse; these findings support the idea of an underlying neurocognitive endophenotype for stimulant drug addiction. 相似文献
12.
Cho AK 《Science (New York, N.Y.)》1990,249(4969):631-634
Ice, which has been described as the drug of the 1990s, is a pure form of (+)methamphetamine hydrochloride; it is more dangerous because of its purity and because it can be inhaled. Taken by this route, the drug causes an effect similar to that from an intravenous dose, and much more intense than that from ingestion. The detailed mechanism of action differs from that of cocaine, but the overall stimulant effect of methamphetamine is similar. Methamphetamine effects, however, persist for hours, whereas cocaine effects are over in minutes. Ice is, therefore, just another agent for abuse by those seeking psychostimulation and, as with cocaine, compulsive abusers of amphetamines consume the drug repeatedly and continuously. Unlike cocaine, methamphetamine is a synthetic compound and is manufactured in illicit laboratories within the United States. 相似文献
13.
J Walsh 《Science (New York, N.Y.)》1971,173(991):32-34
Heroin addiction is the most difficult to control and the most socially destructive form of addiction in America today. Heroin is a fact of life and a cause of death among an increasing number of citizens in America, and it is heroin addiction that must command priority in the struggle against drugs.-President Nixon in his drug message to Congress on 17 June. 相似文献
14.
V. S. Lankin 《Russian Agricultural Sciences》2010,36(1):52-55
A comparative analysis of genetic components of the behavior of domestic pigs toward humans described by an oligogenic model
is carried out. In specialized breeds there is considerable additive genetic variability of this adaptive behavior representing
a new resource for improving productivity and well-being of the animals. 相似文献
15.
V. S. Lankin 《Russian Agricultural Sciences》2013,39(3):271-277
It is established that the contribution of genotype-food motivation interaction is on average more than 60% of the total variation of passive defensive behavior of domestic pigs toward humans. A combined approach to minimizing modification variability of this adaptive behavior adequately describing its genotypic diversity in farm animals is proposed. 相似文献
16.
Lobo MK Covington HE Chaudhury D Friedman AK Sun H Damez-Werno D Dietz DM Zaman S Koo JW Kennedy PJ Mouzon E Mogri M Neve RL Deisseroth K Han MH Nestler EJ 《Science (New York, N.Y.)》2010,330(6002):385-390
The nucleus accumbens is a key mediator of cocaine reward, but the distinct roles of the two subpopulations of nucleus accumbens projection neurons, those expressing dopamine D1 versus D2 receptors, are poorly understood. We show that deletion of TrkB, the brain-derived neurotrophic factor (BDNF) receptor, selectively from D1+ or D2+ neurons oppositely affects cocaine reward. Because loss of TrkB in D2+ neurons increases their neuronal excitability, we next used optogenetic tools to control selectively the firing rate of D1+ and D2+ nucleus accumbens neurons and studied consequent effects on cocaine reward. Activation of D2+ neurons, mimicking the loss of TrkB, suppresses cocaine reward, with opposite effects induced by activation of D1+ neurons. These results provide insight into the molecular control of D1+ and D2+ neuronal activity as well as the circuit-level contribution of these cell types to cocaine reward. 相似文献
17.
O'Doherty A Ruf S Mulligan C Hildreth V Errington ML Cooke S Sesay A Modino S Vanes L Hernandez D Linehan JM Sharpe PT Brandner S Bliss TV Henderson DJ Nizetic D Tybulewicz VL Fisher EM 《Science (New York, N.Y.)》2005,309(5743):2033-2037
Aneuploidies are common chromosomal defects that result in growth and developmental deficits and high levels of lethality in humans. To gain insight into the biology of aneuploidies, we manipulated mouse embryonic stem cells and generated a trans-species aneuploid mouse line that stably transmits a freely segregating, almost complete human chromosome 21 (Hsa21). This "transchromosomic" mouse line, Tc1, is a model of trisomy 21, which manifests as Down syndrome (DS) in humans, and has phenotypic alterations in behavior, synaptic plasticity, cerebellar neuronal number, heart development, and mandible size that relate to human DS. Transchromosomic mouse lines such as Tc1 may represent useful genetic tools for dissecting other human aneuploidies. 相似文献
18.
Boehm C 《Science (New York, N.Y.)》2012,336(6083):844-847
Ancestral Pan, the shared predecessor of humans, bonobos, and chimpanzees, lived in social dominance hierarchies that created conflict through individual and coalitional competition. This ancestor had male and female mediators, but individuals often reconciled independently. An evolutionary trajectory is traced from this ancestor to extant hunter-gatherers, whose coalitional behavior results in suppressed dominance and competition, except in mate competition. A territorial ancestral Pan would not have engaged in intensive warfare if we consider bonobo behavior, but modern human foragers have the potential for full-scale war. Although hunter-gatherers are able to resolve conflicts preemptively, they also use mechanisms, such as truces and peace pacts, to mitigate conflict when the costs become too high. Today, humans retain the genetic underpinnings of both conflict and conflict management; thus, we retain the potential for both war and peace. 相似文献
19.
Cocaine addiction: psychology and neurophysiology 总被引：30，自引：0，他引：30
F H Gawin 《Science (New York, N.Y.)》1991,251(5001):1580-1586
Cocaine was considered incapable of producing dependence in 1980 but was recently proclaimed the drug of greatest national health concern. Recent clinical and preclinical investigations demonstrate that cocaine produces unique abuse and withdrawal patterns that differ from those of other major abused drugs and suggest that long-term cocaine abuse produces neurophysiological alterations in specific systems in the central nervous system that regulate the capacity to experience pleasure. It will be necessary to develop clinically pertinent research models before these findings can be considered definitive, but these evolving ideas have already led to applications of promising experimental treatments for cocaine abuse. 相似文献
20.
de Waal FB 《Science (New York, N.Y.)》2012,336(6083):874-876
The view of humans as violent war-prone apes is poorly supported by archaeological evidence and only partly supported by the behavior of our closest primate relatives, chimpanzees and bonobos. Whereas the first species is marked by xenophobia, the second is relatively peaceful and highly empathic in both behavior and brain organization. Animal empathy is best regarded as a multilayered phenomenon, built around motor mirroring and shared neural representations at basal levels, that develops into more advanced cognitive perspective-taking in large-brained species. As indicated by both observational and experimental studies on our closest relatives, empathy may be the main motivator of prosocial behavior. 相似文献