I.R-D. and A.F. contributed equally to this study.
Antidepressant treatment facilitates dopamine release and drug seeking behavior in a genetic animal model of depression
Article first published online: 15 JUL 2009
© The Authors (2009). Journal Compilation © Federation of European Neuroscience Societies and Blackwell Publishing Ltd
European Journal of Neuroscience
Volume 30, Issue 3, pages 485–492, August 2009
How to Cite
Roth-Deri, I., Friedman, A., Abraham, L., Lax, E., Flaumenhaft, Y., Dikshtein, Y. and Yadid, G. (2009), Antidepressant treatment facilitates dopamine release and drug seeking behavior in a genetic animal model of depression. European Journal of Neuroscience, 30: 485–492. doi: 10.1111/j.1460-9568.2009.06840.x
- Issue published online: 3 AUG 2009
- Article first published online: 15 JUL 2009
- Received 9 February 2009, revised 9 June 2009, accepted 10 June 2009
- nucleus accumbens;
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.