Time-dependent recovery from the effects of 6-hydroxydopamine lesions of the rat nucleus accumbens on cocaine self-administration and the levels of dopamine in microdialysates.
BACKGROUND
Neurotoxin induced lesions of dopamine-releasing neurons that innervate the nucleus accumbens (NAcc) alter cocaine self-administration. In addition, elevated extracellular levels of NAcc dopamine (DA) are thought to be central to the biological mechanisms that underlie this behavior.


OBJECTIVE
This study assessed the long-term effects of 6-hydroxydopamine (6-OHDA) induced lesions of the NAcc on cocaine self-administration and the dialysate levels of dopamine ([DA](d)) in this structure to determine if recovery of drug intake was correlated with the DA response.


METHODS
Rats implanted with jugular catheters and bilateral cannulas were trained to self-administer cocaine and subsequently received bilateral intracranial micro-injections of 6-OHDA or vehicle into the NAcc. The levels of DA and cocaine were determined in microdialysates of the NAcc collected during experimental sessions 6-7, 14-16, 29-30, and 44-46 days post-treatment.


RESULTS
The 6-OHDA induced lesions significantly reduced cocaine self-administration for 3 weeks while vehicle treatment had a moderate effect for the first several days. Cocaine-induced increases in NAcc [DA](d) did not return to sham/vehicle treated control levels for 6 weeks in the lesioned group and DA content in the NAcc was 46% of control at 44 days post-lesion.


CONCLUSIONS
Although dopaminergic lesions of the NAcc produced profound effects on cocaine self-administration, responding recovered to control levels before cocaine-induced increases in NAcc [DA](d) while content of DA in the NAcc did not recover. These data suggest that the plasticity of neuronal systems in the NAcc related to cocaine self-administration and their response following 6-OHDA lesions is more complex than restoration of DAergic tone.
D000818:Animals; D003042:Cocaine / Q000008:administration & dosage*; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D008297:Male; D017551:Microdialysis / Q000379:methods*; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D016627:Oxidopamine / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344; D012646:Self Administration; D013997:Time Factors
D016627:Oxidopamine; D003042:Cocaine; D004298:Dopamine