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

作者：Roth Deri Ilana; Friedman Alexander; Abraham Lital; Lax Elad; Flaumenhaft Yakov; Dikshtein Yahav; Yadid Gal^*

来源：European Journal of Neuroscience, 2009, 30(3): 485-492.

DOI：10.1111/j.1460-9568.2009.06840.x

• addiction
• cocaine
• depression
• dopamine
• nucleus accumbens
• reward

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.

• 出版日期2009-8