Antidepressant treatment facilitates dopamine release and drug seeking behavior in a genetic animal model of depression

• Published in: The European journal of neuroscience 2009-08, Vol.30 (3), p.485-492
• Main Authors: Roth-Deri, Ilana, Friedman, Alexander, Abraham, Lital, Lax, Elad, Flaumenhaft, Yakov, Dikshtein, Yahav, Yadid, Gal
• Format: Article
• Language: English
• Subjects: addiction; Animals; Antidepressive Agents - pharmacology; Autoradiography; Behavior, Addictive - drug therapy; Behavior, Addictive - metabolism; Behavior, Addictive - physiopathology; Behavior, Animal - drug effects; cocaine; Cocaine - pharmacology; depression; Depression - drug therapy; Depression - metabolism; Depression - physiopathology; Disease Models, Animal; dopamine; Dopamine - secretion; Dopamine Uptake Inhibitors - pharmacology; Microdialysis; nucleus accumbens; Nucleus Accumbens - drug effects; Nucleus Accumbens - metabolism; Rats; reward
• ISSN: 0953-816X; 1460-9568
• DOI: 10.1111/j.1460-9568.2009.06840.x

Anhedonia and lack of motivation are core symptoms of depression. In contrast, hyper‐motivation and euphoria characterize intoxicated states. In order to explore the relationship between these two behavioral states we examined cocaine self‐administration tasks in an animal model of depression [Flinders Sensitive Line (FSL) rats]. We found that FSL rats exhibit sub‐sensitivity in their cocaine‐seeking behavior, which was normalized following a chronic treatment with the antidepressant desipramine. However, when the cocaine dosage was increased, FSL rats demonstrated a similar cocaine‐seeking behavior to that of controls. In light of dopamine’s central role in modulating cocaine reinforcement, we examined dopaminergic neurotransmission in the nucleus accumbens, a brain region implicated in the rewarding and hedonic effects of substances of misuse. FSL rats exhibited low but dose‐dependent increases in extracellular levels of dopamine in the nucleus accumbens after acute intravenous cocaine injection. Furthermore, by using the dopamine transporter blocker GBR‐12909 we were able to demonstrate that the low extracellular dopamine levels, observed in FSL rats, were a consequence of low dopamine release in the nucleus accumbens, as opposed to the possibility of increased uptake. Treatment of FSL rats with the antidepressant desipramine raised cocaine‐ and GBR‐12909‐induced dopamine release to the level of controls. This treatment also resulted in increased cocaine‐seeking behavior.