Related Experiment Video
Updated: Jun 11, 2026

A Conditioned Place Preference Protocol for Measuring Incubation of Craving in Rats
Published on: November 6, 2018
Emergence of dormant conditioned incentive approach by conditioned withdrawal in nicotine addiction
1Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York 10461, USA. noboru.hiroi@einstein.yu.edu
Background:
Nicotine is one of the determinants for the development of persistent smoking, and this maladaptive behavior is characterized by many symptoms, including withdrawal and nicotine seeking. The process by which withdrawal affects nicotine seeking is poorly understood.
Method:
The impact of a withdrawal-associated cue on nicotine (.2 mg/kg)-conditioned place preference was assessed in male C57BL/6J mice (n = 8-17/group). To establish a cue selectively associated with withdrawal distinct from those associated with nicotine, a tone was paired with withdrawal in their home cages; mice were chronically exposed to nicotine (200 μg/mL for 15 days) from drinking water in their home cages and received the nicotinic acetylcholine receptor antagonist mecamylamine (2.5 mg/kg) to precipitate withdrawal in the presence of a tone. The effect of the withdrawal-associated tone on nicotine-conditioned place preference was then evaluated in the place-conditioning apparatus after a delay, when nicotine-conditioned place preference spontaneously disappeared.
Results:
A cue associated with precipitated withdrawal reactivated the dormant effect of nicotine-associated cues on conditioned place preference. This effect occurred during continuous exposure to nicotine but not during abstinence.
Conclusions:
A conditioned withdrawal cue could directly amplify the incentive properties of cues associated with nicotine. This observation extends the contemporary incentive account of the role of withdrawal in addiction to cue-cue interaction.
Related Concept Videos
Instinctive Drift
Drug Dependence
CNS Depressants: Alcohol and Nicotine
Drugs Acting on Autonomic Ganglia: Stimulants
Ganglionic stimulants activate NM nicotinic receptors in autonomic ganglia, falling into two categories: nicotine mimetics [e.g., lobeline, dimethylpiperazine, tetramethylammonium] and muscarinic receptor agonists [e.g., muscarine, methacholine]. The first category's action is rapid and blocked by nicotinic receptor antagonists, while the second category's action is delayed and blocked by atropine-like agents. Nicotine, an alkaloid, affects the heart rate by stimulating sympathetic or...
Drug Abuse and Addiction: Pharmacological Phenomena
Operant Conditioning Intervention
In operant conditioning, behaviors that are...
