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

Ilana Roth-Deri, Alexander Friedman, Lital Abraham, Elad Lax, Yakov Flaumenhaft, Yahav Dikshtein, Gal Yadid

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


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.

Original languageEnglish
Pages (from-to)485-492
Number of pages8
JournalEuropean Journal of Neuroscience
Issue number3
StatePublished - Aug 2009
Externally publishedYes


  • Addiction
  • Cocaine
  • Depression
  • Dopamine
  • Nucleus accumbens
  • Reward


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