Evidence for Addiction-like Behavior in the Rat

Although the voluntary intake of drugs of abuse is a behavior largely preserved throughout phylogeny, it is currently unclear whether pathological drug use (“addiction”) can be observed in species other than humans. Here, we report that behaviors that resemble three of the essential diagnostic criteria for addiction appear over time in rats trained to self-administer cocaine. As in humans, this addiction-like behavior is present only in a small proportion of subjects using cocaine and is highly predictive of relapse after withdrawal. These findings provide a new basis for developing a true understanding and treatment of addiction.

[1]  K. Berridge,et al.  The neural basis of drug craving: An incentive-sensitization theory of addiction , 1993, Brain Research Reviews.

[2]  H. de Wit,et al.  Individual differences in the reinforcing and subjective effects of amphetamine and diazepam. , 1986, Drug and alcohol dependence.

[3]  Barry J. Everitt,et al.  Psychomotor Stimulant Addiction: A Neural Systems Perspective , 2002, The Journal of Neuroscience.

[4]  Y. Shaham,et al.  The reinstatement model of drug relapse: history, methodology and major findings , 2003, Psychopharmacology.

[5]  J. Homberg,et al.  Enhanced motivation to self‐administer cocaine is predicted by self‐grooming behaviour and relates to dopamine release in the rat medial prefrontal cortex and amygdala , 2002, The European journal of neuroscience.

[6]  T. Robbins,et al.  Differential control over cocaine-seeking behavior by nucleus accumbens core and shell , 2004, Nature Neuroscience.

[7]  R. Wise.  Brain Reward Circuitry Insights from Unsensed Incentives , 2002, Neuron.

[8]  M. Le Moal,et al.  Vertical Shifts in Self-Administration Dose–Response Functions Predict a Drug-Vulnerable Phenotype Predisposed to Addiction , 2000, The Journal of Neuroscience.

[9]  P. Madden,et al.  Early reactions to cannabis predict later dependence. , 2003, Archives of general psychiatry.

[10]  T. Robbins,et al.  Impulsive Choice Induced in Rats by Lesions of the Nucleus Accumbens Core , 2001, Science.

[11]  S. Watanabe,et al.  Reinforcing effects of methamphetamine in planarians , 2000, Neuroreport.

[12]  B. Pitt.  Psychopharmacology , 1968, Mental Health.

[13]  S. Hyman,et al.  Addiction and the brain: The neurobiology of compulsion and its persistence , 2001, Nature Reviews Neuroscience.

[14]  S. Young,et al.  Substance-dependent, conduct-disordered adolescent males: severity of diagnosis predicts 2-year outcome. , 1998, Drug and alcohol dependence.

[15]  M. Le Moal,et al.  Factors that predict individual vulnerability to amphetamine self-administration. , 1989, Science.

[16]  R. Pickens,et al.  Self-administration of d-amphetamine by rats , 2004, Psychopharmacologia.

[17]  M. Enoch,et al.  Pharmacogenomics of Alcohol Response and Addiction , 2003, American journal of pharmacogenomics : genomics-related research in drug development and clinical practice.

[18]  G. Aghajanian,et al.  Molecular and cellular basis of addiction. , 1997, Science.

[19]  J. R. Weeks,et al.  Experimental Morphine Addiction: Method for Automatic Intravenous Injections in Unrestrained Rats , 1962, Science.

[20]  F. Holsboer,et al.  Anxiety: a potential predictor of vulnerability to the initiation of ethanol self-administration in rats , 1995, Psychopharmacology.

[21]  J. Woods,et al.  Morphine: Conditioned Increases in Self-Administration in Rhesus Monkeys , 1969, Science.

[22]  T. Thompson,et al.  Self administration of and behavioral dependence on drugs. , 1969, Annual review of pharmacology.

[23]  S. M. Stone,et al.  The development of an ethanol model using social insects I: behavior studies of the honey bee (Apis mellifera L.). , 2000, Alcoholism, clinical and experimental research.

[24]  Jane Stewart,et al.  Stress-induced relapse to heroin and cocaine seeking in rats: a review , 2000, Brain Research Reviews.

[25]  N. R. Richardson,et al.  Progressive ratio schedules in drug self-administration studies in rats: a method to evaluate reinforcing efficacy , 1996, Journal of Neuroscience Methods.

[26]  W. DeJong.  Relapse prevention: an emerging technology for promoting long-term drug abstinence. , 1994, The International journal of the addictions.

[27]  D. Wilkin,et al.  Neuron , 2001, Brain Research.

[28]  G F Koob,et al.  Drug abuse: hedonic homeostatic dysregulation. , 1997, Science.

[29]  S. Goldberg,et al.  Behavioral analysis of drug dependence , 1986 .