Inhibition of protein kinase mzeta (PKMζ) in the mesolimbic system alters cocaine sensitization in rats
Joint Authors
Velez Hernandez, Maria E.
Vazquez Torres, Rafael
Velasquez Martinez, Maria C.
Jimenez, Lincoln
Baez, Frankie
Sacktor, Todd C.
Jimenez-Rivera, Carlos A.
Source
Journal of Drug and Alcohol Research
Issue
Vol. 2, Issue 2013 (31 Dec. 2013), pp.1-12, 12 p.
Publisher
Publication Date
2013-12-31
Country of Publication
Egypt
No. of Pages
12
Main Subjects
Abstract EN
Chronic cocaine use produces long-lasting changes in reward circuits that may underlie the transition from casual to compulsive patterns of drug use.
Although strong neuroadaptations within the mesocorticolimbic system are known to occur, the specific role of these drug-induced plasticities on sensitization remains to be elucidated.
Here we investigate whether PKMζ, a protein involved in maintaining long-term potentiation (LTP), plays a role in these cocaine-induced changes in synaptic strengthening.
We performed whole-cell voltage clamp recordings of putative ventral tegmental area (VTA) dopamine (DA) cells 24 hours after 5 days of 15mg/kg i.p.
cocaine or isovolumetric saline injections.
We observed that superfusion of 5 μMZIP (PKMζ inhibitory peptide) decreased AMPA currents and AMPA/NMDA ratios only in cocaine sensitized rats.
In vivo ZIP microinfusions (10 nmol) into the VTA after cocaine sensitization decreased locomotor activity on a subsequent cocaine challenge only if ZIP is given before the withdrawal period.
On the other hand, ZIP microinfusions into the nucleus accumbens (NAc) core after a 7-day withdrawal period disrupt the expression of locomotor sensitization.
The present data provide a potentially relevant region, and timespecific PKMζ-dependent brain mechanism that enables sensitization.
Our results support the vision that addiction involves a pathological learning process.
They imply that if this synaptic strengthening is reversed, changes in the behavioral response may also be overturned.
American Psychological Association (APA)
Velez Hernandez, Maria E.& Vazquez Torres, Rafael& Velasquez Martinez, Maria C.& Jimenez, Lincoln& Baez, Frankie& Sacktor, Todd C.…[et al.]. 2013. Inhibition of protein kinase mzeta (PKMζ) in the mesolimbic system alters cocaine sensitization in rats. Journal of Drug and Alcohol Research،Vol. 2, no. 2013, pp.1-12.
https://search.emarefa.net/detail/BIM-687314
Modern Language Association (MLA)
Vazquez Torres, Rafael…[et al.]. Inhibition of protein kinase mzeta (PKMζ) in the mesolimbic system alters cocaine sensitization in rats. Journal of Drug and Alcohol Research Vol. 2 (2013), pp.1-12.
https://search.emarefa.net/detail/BIM-687314
American Medical Association (AMA)
Velez Hernandez, Maria E.& Vazquez Torres, Rafael& Velasquez Martinez, Maria C.& Jimenez, Lincoln& Baez, Frankie& Sacktor, Todd C.…[et al.]. Inhibition of protein kinase mzeta (PKMζ) in the mesolimbic system alters cocaine sensitization in rats. Journal of Drug and Alcohol Research. 2013. Vol. 2, no. 2013, pp.1-12.
https://search.emarefa.net/detail/BIM-687314
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references : p. 10-12
Record ID
BIM-687314