Why does the rapid delivery of drugs to the brain promote addiction?

doi:10.1016/j.tips.2004.12.007

Trends in Pharmacological Sciences

Volume 26, Issue 2, February 2005, Pages 82-87

https://doi.org/10.1016/j.tips.2004.12.007 Get rights and content

It is widely accepted that the more rapidly drugs of abuse reach the brain the greater their potential for addiction. This might be one reason why cocaine and nicotine are more addictive when they are smoked than when they are administered by other routes. Traditionally, rapidly administered drugs are thought to be more addictive because they are more euphorigenic and/or more reinforcing. However, evidence for this is not compelling. We propose an alternative (although not mutually exclusive) explanation based on the idea that the transition to addiction involves drug-induced plasticity in mesocorticolimbic systems, changes that are manifested behaviourally as psychomotor and incentive sensitization. Recent evidence suggests that rapidly administered cocaine or nicotine preferentially engage mesocorticolimbic circuits, and more readily induce psychomotor sensitization. We conclude that rapidly delivered drugs might promote addiction by promoting forms of neurobehavioural plasticity that contribute to the compulsive pursuit of drugs.

Section snippets

Greater euphoria?

Two complimentary explanations have been proposed to account for the relationship between the rate of drug delivery and the addictive potential of drugs. The first explanation suggests that rapidly administered drugs promote the transition to addiction because they are more euphorigenic 4, 6. Indeed, ratings of subjective pleasurable effects are more immediate and more intense when addicting drugs are delivered rapidly. For example, self-reports of a ‘high’, pleasantness and drug-liking are

The search for an alternative explanation: rate of drug delivery and psychomotor sensitization

If neither an increase in euphoria nor an increase in reinforcing effects fully accounts for why rapidly administered drugs are potentially more addictive, what does? One possibility arises from the idea that addiction is due, at least in part, to the ability of drugs of abuse to reorganize brain regions involved in reward and motivation, such as the dorsal and ventral striatum, and brain regions involved in the inhibitory control of behaviour, such as the prefrontal cortex 15, 27, 28, 29, 30,

The influence of the rate of drug delivery on the neurobiological impact of drugs

Given that it is so widely accepted that the rapid delivery of drugs to the brain promotes addiction, it is surprising that only few studies have examined how the rate of drug delivery influences the neurobiological effects of drugs. The few studies to examine dopamine (DA) activity have not revealed large effects. For example, in vivo microdialysis used to quantify DA overflow in the nucleus accumbens of rats following intravenous infusions of a fixed dose of cocaine delivered over 6 s or 150 s

Concluding remarks

These findings demonstrate that differences in the rate at which addicting drugs are administered determine their ability to produce psychomotor sensitization, and presumably its associated adaptations in the brain. These results represent a first step in characterizing an as yet unknown and unappreciated relationship between the rate of drug delivery and the ability of addicting drugs to produce forms of neurobehavioural plasticity that might lead to excessive incentive motivation for drugs

Acknowledgements

Our work has been supported by grants from NIDA (R37 DA04294/K05 DA00473/T32 DA07267).

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Trends in Pharmacological Sciences

Why does the rapid delivery of drugs to the brain promote addiction?

Section snippets

Greater euphoria?

The search for an alternative explanation: rate of drug delivery and psychomotor sensitization

The influence of the rate of drug delivery on the neurobiological impact of drugs

Concluding remarks

Acknowledgements

Brain Res. Brain Res. Rev.

Pharmacol. Biochem. Behav.

Eur. J. Pharmacol.

Neuropharmacology

Pharmacol. Biochem. Behav.

Neurosci. Biobehav. Rev.

Life Sci.

J. Neurosci. Methods

Neuroscience

Brain Res.

Trends Neurosci.

Behav. Brain Res.

Behavioral and biological factors associated with individual vulnerability to psychostimulant abuse

NIDA Res. Monogr.

A Handbook on Drug and Alcohol Abuse: The Biomedical Aspects

Severity of dependence and route of administration of heroin, cocaine and amphetamines

Br. J. Addict.

Crack cocaine and cocaine hydrochloride. Are the differences myth or reality?

J. Am. Med. Assoc.

Nicotine delivery kinetics and abuse liability

J. Consult. Clin. Psychol.

Subjective and behavioral effects of diazepam depend on its rate of onset

Psychopharmacology (Berl.)

Acute systemic effects of cocaine in man: a controlled study by intranasal and intravenous routes

Science

Comparison of intravenous and intranasal heroin self-administration by morphine-maintained humans

Psychopharmacology (Berl.)

Injection duration of cocaine in humans

Fed. Proc.

Effect of intravenous injection speed on responses to cocaine and hydromorphone in humans

Psychopharmacology (Berl.)

Effects of infusion rate of intravenously administered morphine on physiological, psychomotor, and self-reported measures in humans

J. Pharmacol. Exp. Ther.

Comparison of acute behavioral effects of sustained-release and immediate-release methylphenidate

Exp. Clin. Psychopharmacol.

Rate of increase of plasma drug level influences subjective response in humans

Psychopharmacology (Berl.)

Intravenous drug injection habits: drug users' self-reports versus researchers' perception

Pharmacology

The reinforcing and subjective effects of morphine in post-addicts: a dose–response study

J. Pharmacol. Exp. Ther.

Relationship between self-reported drug effects and their reinforcing effects: studies with stimulant drugs

NIDA Res. Monogr.