Abstract:
BACKGROUND:Several theories propose alternative explanations for drug addiction. OBJECTIVES:We propose a general theory of transition to addiction that synthesizes knowledge generated in the field of addiction into a unitary explanatory frame. MAJOR PRINCIPLES OF THE THEORY:Transition to addiction results from a sequential three-step interaction between: (1) individual vulnerability; (2) degree/amount of drug exposure. The first step, sporadic recreational drug use is a learning process mediated by overactivation of neurobiological substrates of natural rewards that allows most individuals to perceive drugs as highly rewarding stimuli. The second, intensified, sustained, escalated drug use occurs in some vulnerable individuals who have a hyperactive dopaminergic system and impaired prefrontal cortex function. Sustained and prolonged drug use induces incentive sensitization and an allostatic state that makes drugs strongly wanted and needed. Habit formation can also contribute to stabilizing sustained drug use. The last step, loss of control of drug intake and full addiction, is due to a second vulnerable phenotype. This loss-of-control-prone phenotype is triggered by long-term drug exposure and characterized by long-lasting loss of synaptic plasticity in reward areas in the brain that induce a form of behavioral crystallization resulting in loss of control of drug intake. Because of behavioral crystallization, drugs are now not only wanted and needed but also pathologically mourned when absent. CONCLUSIONS:This general theory demonstrates that drug addiction is a true psychiatric disease caused by a three-step interaction between vulnerable individuals and amount/duration of drug exposure.
journal_name
Psychopharmacology (Berl)journal_title
Psychopharmacologyauthors
Piazza PV,Deroche-Gamonet Vdoi
10.1007/s00213-013-3224-4subject
Has Abstractpub_date
2013-10-01 00:00:00pages
387-413issue
3eissn
0033-3158issn
1432-2072journal_volume
229pub_type
杂志文章abstract:RATIONALE:Previous studies have shown that buspirone, a partial 5-HT(1A) receptor agonist, produces antinociceptive effects in rats and mice; Ca(2+) plays a critical role as a second messenger in mediating nociceptive transmission. 5-HT(1A) receptors have been proven to be coupled functionally with various types of Ca(...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-002-1327-4
更新日期:2003-03-01 00:00:00
abstract:RATIONALE:Serotonin and especially serotonin 2A (5-HT(2A)) receptor signaling are important in the etiology and treatment of schizophrenia and affective disorders. We previously reported a novel 5-HT(2A) receptor effector, increased transglutaminase (TGase)-catalyzed transamidation, and activation of the small G protei...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-010-1984-7
更新日期:2011-02-01 00:00:00
abstract:RATIONALE:The drug discrimination procedure has proven to be a valuable tool for studying the mechanism of action of psychoactive drugs. Recently, mice with targeted gene mutations have been developed that may also prove useful in evaluating the role of specific receptors in mediating the actions of drugs. We were inte...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-002-1252-6
更新日期:2003-02-01 00:00:00
abstract:RATIONALE:Previous work has shown that clozapine suppressed tacrine-induced jaw movements at lower doses than those required for suppression of lever pressing. OBJECTIVE:The novel atypical antipsychotic olanzapine was assessed in these behavioral tests. METHODS:The effect of acute olanzapine on the suppression of tac...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s002130051063
更新日期:1999-08-01 00:00:00
abstract::Three recently arrived drug naive Cebus apella monkeys with "spontaneous" stereotyped oral movements were treated with apomorphine and haloperidol using a wide dose range. Low doses of apomorphine (0.05-0.1 mg/kg) suppressed the oral stereotypies without affecting normal behaviour such as grooming and scratching. High...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00428423
更新日期:1985-01-01 00:00:00
abstract::The effect of the dopamine receptor antagonist haloperidol on the development of sensitization to ethanol-induced increases in locomotor activity was examined in DBA/2J mice. In Experiment 1, different groups of mice were given saline or ethanol (2 g/kg) immediately before each of four locomotor activity sessions (48-...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF02245821
更新日期:1995-08-01 00:00:00
abstract:RATIONALE:Clinically, nicotine improves attention, but this has proven difficult to demonstrate preclinically. We tested nicotine in Sprague-Dawley (SD) and Lister hooded (LH) rats in the five-choice serial reaction time task. Since SD rats demonstrate lower asymptotic performance than LH rats, we surmised that nicotin...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s002130000605
更新日期:2001-02-01 00:00:00
abstract::The performance of healthy volunteer subjects on an auditory latent inhibition (LI) paradigm was assessed following administration of a single oral dose of d-amphetamine or placebo. It was predicted that a low (5 mg), but not a high (10 mg), dose of d-amphetamine would disrupt LI. The prediction was supported with lef...
journal_title:Psychopharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/BF02245170
更新日期:1992-01-01 00:00:00
abstract:RATIONALE:Functional interactions between limbic regions that process emotions and frontal networks that guide response functions provide a substrate for emotional cues to influence behavior. Stimulation of postsynaptic α₂ adrenoceptors enhances the function of prefrontal regions in these networks. However, the impact ...
journal_title:Psychopharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1007/s00213-012-2893-8
更新日期:2013-03-01 00:00:00
abstract::The effects of diazepam (10 mg orally) on the responding of normal human volunteers was studied in a procedure that involved the maintenance of operant behavior by monetary reinforcement and its suppression by monetary loss (punishment). Diazepam produced an antipunishment effect as shown by an increase in behavior su...
journal_title:Psychopharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/BF00426457
更新日期:1981-01-01 00:00:00
abstract::Continuous low-level (0.825 mg/kg/h for 20 h) administration of AP through SC in-dwelling silicone reservoirs in the rat induced behavioral and biochemical changes that were similar to those induced by low levels (0.1 mg/kg) of acutely administered AP (decreased behavioral activity and decreased dopamine metabolism in...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00427314
更新日期:1985-01-01 00:00:00
abstract::Maternal pup searching behaviour of lactating house mice treated with apomorphine, haloperidol or saline was examined on a running board with a central depression as a nest. Pup searching was elicited by artificial ultrasonic stimuli: a female moved out from the nest either towards a 50 kHz tone (key stimulus) which i...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00174523
更新日期:1988-01-01 00:00:00
abstract:RATIONALE:Although newer interview methods such as Structured Interview Guide for the Montgomery-Asberg Depression Rating Scale (SIGMA; MADRS) with audiotaping and Rater Applied Performance Scale (RAPS) appraisal have been introduced to improve reliability of ratings in antidepressant clinical trials, there is limited ...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-014-3584-4
更新日期:2014-11-01 00:00:00
abstract:RATIONALE:Greater incidence of anxiety and depressive disorders of women compared to men may be due in part to progesterone (P) and its neuroactive metabolite, 5alpha-pregnan-3alpha-ol-20-one (3alpha,5alpha-THP), acting in limbic regions, such as the amygdala. OBJECTIVE:If P's metabolism via 5alpha-reduction to 3alpha...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-005-0100-x
更新日期:2006-06-01 00:00:00
abstract::The central effects of acetylsalicylic acid (ASA) are discussed controversially. In animal models, it has been shown that ASA can interact with the central serotonergic and catecholaminergic neuronal system. However, the relevance of this interaction for humans is still unknown. We performed a study on the influence o...
journal_title:Psychopharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/s002130050683
更新日期:1998-08-01 00:00:00
abstract:RATIONALE:Kratom is proposed to exhibit therapeutic potential as an opium substitute, but little is known about its dependence-producing profile, particularly of its main psychoactive compound, mitragynine (MG). OBJECTIVES:This study examined the dependence-producing effects of MG using operant-scheduled behaviour in ...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-019-05418-6
更新日期:2020-03-01 00:00:00
abstract:RATIONALE:Lysergic acid diethylamide (LSD) differs from other types of hallucinogens in that it possesses direct dopaminergic effects. The exact nature of this component has not been elucidated. OBJECTIVE:The present study sought to characterize the effects of several dopamine D(4) agonists and antagonists on the disc...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-008-1238-0
更新日期:2009-04-01 00:00:00
abstract::Doses of eight phenylethylamines were substituted for cocaine on a drug-maintained behavior baseline in baboons. Intravenous infusions of drug were contingent upon completion of 160 lever presses (a 160-response fixed-ratio schedule; FR 160). A 3-h time-out period followed each infusion, permitting a maximum of 8 infu...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00426841
更新日期:1976-11-24 00:00:00
abstract:RATIONALE:Latent inhibition (LI), namely, poorer performance on a learning task involving a previously pre-exposed non-reinforced stimulus, is disrupted in the rat by the dopamine (DA) releaser amphetamine which produces and exacerbates psychotic (positive) symptoms, and this is reversed by treatment with typical and a...
journal_title:Psychopharmacology
pub_type: 杂志文章,评审
doi:10.1007/s00213-002-1313-x
更新日期:2003-09-01 00:00:00
abstract::Adult hooded rats exposed to a repeated maternal separation procedure during the neonatal period showed a blunted expression of locomotor hyperactivity conditioned to the presentation of the daily food ration. We have demonstrated that the expression of food-conditioned anticipatory hyperactivity is sensitive to the r...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF02246414
更新日期:1996-07-01 00:00:00
abstract:INTRODUCTION:Understanding an individual's vulnerability to drug addiction has important implications for the development of effective personal treatment plans. Although theories acknowledge impulsive behaviour as a key component of drug addiction, little is known about the influence of trait impulsivity on an individu...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-013-3270-y
更新日期:2014-02-01 00:00:00
abstract:OBJECTIVE:To compare matched paliperidone-ER- and olanzapine-treated schizophrenic patients on measures of glucose and lipid metabolism. METHODS:Eighty hospitalized patients with schizophrenia (DSM-IV) were randomly assigned to treatment with paliperidone ER or olanzapine for a period of 12 weeks. At baseline and ever...
journal_title:Psychopharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1007/s00213-013-3073-1
更新日期:2013-11-01 00:00:00
abstract:RATIONALE:The metabotropic glutamate (mGlu5) receptor subtype 5 antagonist MPEP attenuates self-administration of numerous drugs of abuse. OBJECTIVES:The purpose of the present study was to explore whether MPEP-induced decreases in nicotine and cocaine self-administration reflect attenuation of the reinforcing and inc...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-004-2070-9
更新日期:2005-04-01 00:00:00
abstract::Because of the increasing demand for refined techniques to record drug-induced motoric changes, we designed and evaluated a computer monitoring system with continuous measurement of different parameters of rat motor activity. This system is particularly useful for chronic drug studies because it can characterize patte...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00432113
更新日期:1983-01-01 00:00:00
abstract:RATIONALE:Several lines of evidence have indicated that the central histaminergic system might be involved in learning and memory OBJECTIVES:The aim of the present study was to ascertain the impact on memory processes of putative histaminergic-cholinergic interactions in the nucleus basalis magnocellularis (NBM) of th...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s002130100892
更新日期:2002-01-01 00:00:00
abstract::The effects of olanzapine [LY 170053; 2-methyl-4-(4-methyl-1-piperazinyl)-10H-thieno[2, 3b] [1,5]benzodiazepine), a potential atypical antipsychotic, were determined in pigeons whose keypeck responding was punished. These effects were compared to the anxiolytic agents chlordiazepoxide and pentobarbital, and to other a...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF02246153
更新日期:1995-05-01 00:00:00
abstract::Dopaminergic involvement in the regulation of operant behavior was examined by monitoring responding after administration of different dopaminergic agonists. A chain schedule of reinforcement was used to classify the effects of these agonists in long-tailed macaques (Macaca fascicularis). The schedule included the fol...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00429014
更新日期:1983-01-01 00:00:00
abstract:RATIONALE:The effects of acute bouts of physical activity (PA) on Strength of Desire (SoD) and Desire to Smoke (DtS) using individual participant data (IPD) from 19 acute randomised controlled studies were quantified. However, there is a need to identify factors influencing this relationship. OBJECTIVES:To understand ...
journal_title:Psychopharmacology
pub_type: 杂志文章,meta分析,评审
doi:10.1007/s00213-014-3450-4
更新日期:2014-04-01 00:00:00
abstract:RATIONALE:Several recent studies have focused on glutamate modulating agents for symptoms relief in schizophrenia, especially negative symptoms which are resistant to conventional therapies. OBJECTIVES:We aimed to assess the efficacy and tolerability of riluzole, an anti-glutamate agent with neuroprotective properties...
journal_title:Psychopharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1007/s00213-013-3261-z
更新日期:2014-02-01 00:00:00
abstract:RATIONALE:A number of studies have indicated a relationship between the intake of palatable foods or fluids and drug self-administration. OBJECTIVES:Two experiments were conducted to determine whether the intake of sucrose or fat was related to subsequent cocaine self-administration. METHODS:In separate groups of rat...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s002130000375
更新日期:2000-04-01 00:00:00