Related Experiment Video
Updated: Jun 22, 2026

A Protocol for Measuring Cue Reactivity in a Rat Model of Cocaine Use Disorder
Published on: June 18, 2018
Individual differences in dopamine cell neuroadaptations following cocaine self-administration
James E McCutcheon1, Francis J White, Michela Marinelli
1Department of Cellular and Molecular Pharmacology, Rosalind Franklin University of Medicine and Science, The Chicago Medical School, North Chicago, Illinois 60064, USA.
Background:
Addictive drugs produce neuroadaptations in dopamine neurons of the ventral tegmental area. It is unknown if individual differences in these neuroadaptive responses can account for naturally occurring differences in drug addiction liability.
Methods:
To study this question, we took advantage of high-responder (HR) and low-responder (LR) rats, a population that exhibits spontaneous differences in several models of addiction. High-responder and LR rats were allowed to self-administer saline or a high dose of cocaine (500 microg/kg/infusion) over a brief period, to normalize drug intake across individuals. Drug-induced changes in the baseline activity of ventral tegmental area dopamine neurons were recorded after various periods of withdrawal.
Results:
All rats developed self-administration behavior and showed similar levels of drug intake. Withdrawal from cocaine self-administration increased dopamine cell firing and bursting in all animals. However, these changes in firing rates and patterns were more persistent in HR than in LR rats.
Conclusions:
These results demonstrate individual differences in the duration of drug-induced neuroadaptations in dopamine neurons of the ventral tegmental area. More persistent elevation of dopamine cell activity and reduced capacity to return to baseline levels may be an important factor contributing to the development of addiction in "at-risk" individuals.
Related Concept Videos
Drug Abuse and Addiction: Pharmacological Phenomena
CNS Stimulants: Cocaine, Amphetamines and Cannabinoids
Attention-Deficit/Hyperactivity Disorder
Diagnostic Criteria and Symptoms
To diagnose ADHD, symptoms must manifest before age 12 and be evident across multiple settings.
Drugs Affecting Neurotransmitter Synthesis
Adrenergic Agonists: Indirect-Acting Agents
One mechanism involves depleting stored catecholamines by displacing them from synaptic vesicles. These agents, known as "displacers," are transported into vesicles at the expense of noradrenaline. Examples include amphetamine and tyramine, which lack a catechol moiety, resulting in prolonged action, improved oral bioavailability, and...

