Phosphodiesterase 10A regulates alcohol and saccharin self-administration in rats.
paper
Cited
Public
Unavailable
- Authors
- Logrip, Marian L; Vendruscolo, Leandro F; Schlosburg, Joel E; Koob, George F; Zorrilla, Eric P
- Year
- 2014
- Journal
- Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
- PMID
- 24549104
- DOI
- 10.1038/npp.2014.20
- PMCID
- PMC4023146
A history of stress produces increases in rodent relapse-like alcohol self-administration behavior and regional brain gene expression of phosphodiesterase 10A (PDE10A), a dual-specificity cyclic adenosine monophosphate/cyclic guanosine monophosphate-inhibiting enzyme. Here, we tested the hypothesis that administration of TP-10, a specific PDE10A inhibitor, would reduce alcohol self-administration in conditions predisposing to elevated self-administration. TP-10 administration dose-dependently (0.562, 1.0 mg/kg; subcutaneously) reduced relapse-like alcohol self-administration regardless of stress history enhancement of relapse-like behavior. TP-10 also reduced alcohol self-administration in genetically alcohol-preferring rats, as well as in alcohol-non-dependent and -dependent rats. Effective systemic TP-10 doses did not alter alcohol pharmacokinetics, significantly reduce motor activity or intrabout operant response speed, or promote a conditioned place aversion. TP-10 also reduced saccharin self-administration, suggesting a general role for PDE10A in the self-administration of reinforcing substances. PDE10A inhibition in the dorsolateral striatum, but not the nucleus accumbens, reduced alcohol self-administration. Taken together, the results implicate dorsolateral striatum PDE10A in facilitating alcohol intake and support further investigation of PDE10A systems in the pathophysiology and potential treatment of substance use disorders.
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