Antidepressant treatment facilitates dopamine release and drug seeking behavior in a genetic animal model of depression.
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.
Roth-Deri
Ilana
I
Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.
Friedman
Alexander
A
Abraham
Lital
L
Lax
Elad
E
Flaumenhaft
Yakov
Y
Dikshtein
Yahav
Y
Yadid
Gal
G
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001345:Autoradiography; D016739:Behavior, Addictive / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D001522:Behavior, Animal / Q000187:drug effects; D003042:Cocaine / Q000494:pharmacology; D003863:Depression / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D017551:Microdialysis; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D051381:Rats
D000928:Antidepressive Agents; D018765:Dopamine Uptake Inhibitors; D003042:Cocaine; D004298:Dopamine