کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6258674 | 1612979 | 2013 | 9 صفحه PDF | دانلود رایگان |
- We studied the effects of cocaine in MK and PTN genetically deficient mice.
- Acquisition of cocaine-induced CPP was similar in MKâ/â, PTNâ/â and wild type mice.
- MK is a novel genetic factor with a role in the extinction of cocaine CPP.
- Phosphorylation of striatal Prdx6 may be involved in the extinction of cocaine CPP.
The neurotrophic factors Midkine (MK) and Pleiotrophin (PTN) have been suggested to modulate drugs of abuse-induced effects. To test this hypothesis, cocaine (10 and 15Â mg/kg)-induced conditioned place preference (CPP) was rendered in PTN knockout (PTNâ/â), MK knockout (MKâ/â) and wild type (WT+/+) mice, and then extinguished after repeated saline injections (distributed in 4 extinction sessions). Cocaine induced a similar CPP in all the three genotypes. We found a significantly increased percentage of MKâ/â mice that did not extinguish cocaine CPP at the end of the extinction sessions. Particularly, 40% of MKâ/â mice did not extinguish cocaine (15Â mg/kg)-induced CPP compared to WT+/+ and PTNâ/â mice (â¼0-6%). Interestingly, we found that a greater magnitude of extinction of CPP after the first extinction session (5 days after last administration of cocaine) correlates with increased tyrosine phosphorylation of the enzyme peroxiredoxin 6 in the dorsal striatum of MKâ/â mice. On the other hand, a greater magnitude of CPP extinction correlates with increased tyrosine phosphorylation of aconitase 2 in the prefrontal cortex of WT+/+ mice. In contrast, a lower magnitude of CPP extinction correlates with increased phosphorylation of aconitase 2 in the prefrontal cortex of PTNâ/â mice, suggesting that the correlation between the tyrosine phosphorylation levels of aconitase 2 and magnitude of CPP extinction depends on the genotype considered. The data demonstrate that MK is a novel genetic factor that plays a role in the extinction of cocaine-induced CPP by mechanisms that may involve specific phosphorylation of striatal peroxiredoxin 6.
Journal: Behavioural Brain Research - Volume 253, 15 September 2013, Pages 223-231