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Updated: May 25, 2026

Assessment of Cocaine-induced Behavioral Sensitization and Conditioned Place Preference in Mice
Published on: February 18, 2016
Stress induces behavioral sensitization, increases nicotine-seeking behavior and leads to a decrease of CREB in the
Rodrigo Molini Leão1, Fábio Cardoso Cruz, Marcelo Tadeu Marin
1Laboratory of Pharmacology, School of Pharmaceutical Sciences, Univ. Estadual Paulista-UNESP, Rod. Araraquara-Jaú Km 1, 14801-902, Araraquara, São Paulo, Brazil.
Variable stress exposure in rats enhanced nicotine-induced locomotor activity and increased drug seeking. This stress exposure also altered molecular pathways in the brain, suggesting a link between stress and addiction vulnerability.
Area of Science:
- Neuroscience
- Behavioral Pharmacology
- Molecular Biology
Background:
- Stress exposure is known to increase drug-seeking behavior and drug intake.
- The precise molecular mechanisms underlying stress-induced changes in drug addiction remain unclear.
- Understanding these mechanisms is crucial for developing effective addiction treatments.
Purpose of the Study:
- To investigate the effects of variable stress exposure on nicotine-induced behaviors in rats.
- To examine the impact of stress on molecular changes in the nucleus accumbens, specifically involving CREB and ERK.
- To assess how prior stress exposure influences nicotine self-administration.
Main Methods:
- Male Wistar rats were subjected to a 10-day variable stress paradigm or left undisturbed (control).
- Locomotor activity was measured after nicotine challenge; brain tissue was analyzed using Western blotting for CREB and ERK.
- Nicotine self-administration was assessed using a progressive ratio schedule and 24-hour binge intake analysis.
Main Results:
- Variable stress exposure resulted in a sensitized locomotor response to nicotine.
- Stress led to decreased levels of cAMP-response element-binding protein (CREB) in the nucleus accumbens.
- Stressed rats exhibited increased breakpoint and nicotine intake during self-administration.
Conclusions:
- Repeated variable stress sensitizes behavioral responses to nicotine and alters key molecular pathways in reward circuitry.
- These findings suggest that stress exposure can increase vulnerability to nicotine addiction.
- Targeting stress-related molecular mechanisms may offer novel therapeutic strategies for substance use disorders.
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