Conditioned nicotine withdrawal profoundly decreases the activity of brain reward systems
by
Kenny PJ, Markou A.
Department of Neuropharmacology,
The Scripps Research Institute,
La Jolla, California 92037.
J Neurosci. 2005 Jun 29;25(26):6208-12.

ABSTRACT

Withdrawal from nicotine decreases the activity of brain reward systems, measured in rats by elevations of intracranial self-stimulation (ICSS) thresholds. This reward deficit is hypothesized to contribute to the persistence of the tobacco habit in tobacco smokers. Accumulating evidence suggests that aspects of drug withdrawal may become conditioned to previously neutral environmental stimuli via pavlovian conditioning processes. Here we investigated whether hedonically neutral stimuli repeatedly paired with nicotine withdrawal gained "affective valence" such that withdrawal-associated conditioned stimuli alone decreased brain reward function. Nicotine-dependent rats were presented with a light/tone conditioned stimulus and injected with the nicotinic receptor antagonist dihydro-beta-erythroidine (DHbetaE; 3 mg/kg) for 4 d consecutively; ICSS thresholds were assessed before and immediately after DHbetaE injection. On the test day, the rats were presented with the conditioned stimulus and injected with saline; next, ICSS thresholds were assessed. During conditioning sessions, DHbetaE elevated reward thresholds, and the magnitude by which thresholds were elevated increased during successive conditioning sessions. These data suggest that withdrawal-associated conditioned stimuli potentiated the magnitude of nicotine withdrawal as their motivational significance increased. Most importantly, on the test day, the conditioned stimulus alone elevated reward thresholds. Similarly, in a separate experiment, withdrawal-associated cues elevated reward thresholds in morphine-dependent rats. These data provide the first empirical verification that conditioned nicotine withdrawal may occur after exposure to withdrawal-paired cues. Moreover, these data demonstrate that withdrawal-paired conditioned stimuli attain negative affective valence and can decrease the activity of brain reward systems, mimicking the reward deficit observed during withdrawal from nicotine and other addictive drugs.

Nicotine
Tobacco
Alcohol
Smoking
Cotinine
Cigarettes
Addicting women
Free-base nicotine
Nicotine : structure
Parkinson's disease
Smoking and MAO-A
Smoking and MAO-B
Nicotine neuroprotection
Cigars, bidis, and kreteks
Nicotine, dopamine and reward
Muscarinic + nicotinic receptors
Bupropion and nicotinic receptors
Bupropion (Zyban) for cigarette smokers
Quitting smoking: the role of antidepressants
Nicotine, pleasure, and reward sensitization

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