Modeling the role of environment in addiction

doi:10.1016/j.pnpbp.2007.08.029

Progress in Neuro-Psychopharmacology and Biological Psychiatry

Volume 31, Issue 8, 15 November 2007, Pages 1639-1653

https://doi.org/10.1016/j.pnpbp.2007.08.029 Get rights and content

Abstract

The aim of this review is to provide an overview of the main types of animal models used to investigate the modulatory role of environment on drug addiction. The environment can alter the responsiveness to addictive drugs in at least three major ways. First, adverse life experiences can make an individual more vulnerable to develop drug addiction or to relapse into drug seeking. Second, neutral environmental cues can acquire, through Pavlovian conditioning, the ability to trigger drug seeking even after long periods of abstinence. Third, the environment immediately surrounding drug taking can alter the behavioral, subjective, and rewarding effects of a given drug, thus influencing the propensity to use the same drug again. We have focused in particular on the results obtained using an animal model we have developed to study the latter type of drug–environment interaction.

Introduction

For more than three decades now, research on drug addiction has mostly focused on the cascade of molecular changes stemming from the actions of drugs at specific binding sites in the brain. This approach has been enormously successful in advancing the field, showing, among other things, that virtually all addictive drugs modulate the activity of the mesotelencephalic dopaminergic system, particularly at the level of the nucleus accumbens (NAc). Any attempt to reduce the behavioral and psychological effects of drugs to the straightforward consequences of ligand–receptor binding, however, risks overlooking the complexity of drug–environment interaction. Indeed, both clinical and preclinical evidence indicate that drug addiction is a multifactorial disorder in which genetic and environmental variables interact in modulating individual responsiveness to addictive drugs (see Anthony and Chen, 2004).

The environment can impinge on the propensity to the abuse drugs in at least three major ways. First, certain life experiences can make an individual more vulnerable to develop drug addiction or to relapse into drug seeking. (Conversely, other types of experience may protect an individual from the risk of becoming drug dependent or to relapse after becoming abstinent.) Second, neutral environmental cues can acquire, through their association with drugs, the ability to trigger drug seeking even after long periods of abstinence. Third, the environment immediately surrounding drug taking can alter the behavioral, subjective, and rewarding effects of a given drug, thus influencing the propensity to use the same drug again.

The aim of this review is to provide a concise overview of the animal models used to investigate these three types of drug–environment interactions, focusing in particular on recent data from the authors' laboratory. In contrast, not even a cursory attempt will be made to review here the formidable literature concerning the behavioral economics of drug seeking (for a review, see Campbell and Carroll, 2000) or the role played by environmental cues in the expression of drug sensitization (Anagnostaras and Robinson, 1996) or in the acquisition of instrumental learning (for a critical appraisal of the neurobiology of instrumental learning, see Cardinal and Everitt, 2004). Furthermore, it is beyond the scope of this review to discuss the role of xenobiotics, including environmental toxins and drugs, in modulating individual vulnerability to drug addiction.

Section snippets

Adverse life experiences

There is a sizeable literature on the association between a history of adverse life experiences and drug addiction. Events as different as sexual abuse/harassment, combat-stress, occupational stress, marriage dissatisfaction, and physical traumas have been linked to the abuse of psychostimulants, opioids, and alcohol (Aro, 1981, Triffleman et al., 1995, Richman et al., 1996, Brown et al., 2006, Jose et al., 2000, Brady et al., 2001, Clark et al., 2001, Price et al., 2004, Ompad et al., 2005,

Conditioning

Research done in the last two decades has shown that environmental stimuli paired with drug taking (or with life events capable of affecting drug taking) can acquire, through associative learning, the ability to elicit responses related to the drug experience or even motivate the behavior directly serving as secondary reinforcers.³

Circumstances of drug taking

Not all environmental factors capable of affecting the effects of addictive drugs can be conceptualized as adverse life experiences. Since the 1960s, albeit sporadically, a number of authors have emphasized the importance of the setting in which drugs are experienced as an important determinant of their behavioral and subjective effects (for example, see Kelleher and Morse, 1968, Zinberg, 1984, Barrett, 1987, Falk and Feingold, 1987). A dramatic example of the role of setting is represented by

Conclusion

Drugs such as heroin, cocaine, and amphetamine have been available on the global market for more than one hundred years. Yet, the geographical distribution of their use has never been homogeneous, each of them being the drug of choice of some individuals in some countries, cities, communities, and neighborhoods, but not in others (Anthony and Chen, 2004, Westermeyer, 2004). Furthermore, their use changes over time, with popularity changing with lifestyle changes. Yet very little is known about

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Review articleModeling the role of environment in addiction

Abstract

Introduction

Section snippets

Adverse life experiences

Conditioning

Circumstances of drug taking

Conclusion

Pharmacol Biochem Behav

Brain Res

Brain Res

Behav Brain Res

Behav Neural Biol

Eur J Pharmacol

Pharmacol Biochem Behav

Pharmacol Biochem Behav

J Subst Abuse Treat

Curr Opin Neurobiol

Brain Res

Neuroscience

Pharmacol Biochem Behav

Biochem Biophys Res Commun

J Subst Abuse Treat

Eur J Pharmacol

Brain Res

Pharmacol Biochem Behav

Neuropsychopharmacology

Drug Alcohol Depend

Neuropsychopharmacology

Neuroscience

Brain Res

Child Abuse Negl

Physiol Behav

Neuropsychopharmacology

Cocaine- but not food-seeking behavior is reinstated by stress after extinction

Psychopharmacology (Berl)

The effect of housing and gender on morphine self-administration in rats

Psychopharmacology (Berl)

Effects of SCH-23390 infused into the amygdala or adjacent cortex and basal ganglia on cocaine seeking and self-administration in rats

Neuropsychopharmacology

Sensitization to the psychostimulant effects of amphetamine: modulation by associative learning

Behav Brain Res

Epidemiology of drug dependence

Stress, morbidity, and health-related behaviour. A five-year follow-up study among metal industry employees

Scand J Soc Med Suppl

Drug-induced neurobehavioral plasticity: the role of environmental context

Behav Pharmacol

The development of sensitization to the psychomotor stimulant effects of amphetamine is enhanced in a novel environment

Psychopharmacology (Berl)

Enduring enhancement of amphetamine sensitization by drug-associated environmental stimuli

J Pharmacol Exp Ther

Amphetamine-induced behavior, dopamine release and c-fos mRNA expression: modulation by environmental novelty

J Neurosci

Environmental modulation of the response to amphetamine: dissociation between changes in behavior and changes in dopamine and glutamate overflow in the rat striatal complex

Psychopharmacology (Berl)

Modulation of morphine sensitization in the rat by contextual stimuli

Psychopharmacology (Berl)

Environmental enrichment decreases intravenous self-administration of amphetamine in female and male rats

Psychopharmacology (Berl)

Nonpharmacological factors determining the behavioral effects of drugs

Local release of GABAergic inhibition in the motor cortex induces immediate-early gene expression in indirect pathway neurons of the striatum

J Neurosci

A role of ventral tegmental area glutamate in contextual cue-induced relapse to heroin seeking

J Neurosci

Activation of group II metabotropic glutamate receptors in the nucleus accumbens shell attenuates context-induced relapse to heroin seeking

Neuropsychopharmacology

The influence of environment on the induction of sensitization to the psychomotor activating effects of intravenous cocaine in rats is dose-dependent

Psychopharmacology (Berl)

Modulatory effect of environmental stimuli on the susceptibility to amphetamine sensitization: a dose–effect study in rats

J Pharmacol Exp Ther

Stress and coping: the roles of ethnicity and gender in substance abuse recovery

J Prev Interv Community

The effect of novelty on amphetamine self-administration in rats classified as high and low responders

Psychopharmacology (Berl)

Acquisition of drug self-administration: environmental and pharmacological interventions

Exp Clin Psychopharmacol

Effects of ketoconazole on the acquisition of intravenous cocaine self-administration under different feeding conditions in rats

Psychopharmacology (Berl)

A role for the prefrontal cortex in stress- and cocaine-induced reinstatement of cocaine seeking in rats

Psychopharmacology (Berl)

Review article
Modeling the role of environment in addiction