Journal article
Rapamycin reduces motivated responding for cocaine and alters GluA1 expression in the ventral but not dorsal striatum
European journal of pharmacology, Vol.784, pp.147-154
05/08/2016
PMID: 27181066
Metrics
21 Record Views
UN Sustainable Development Goals (SDGs)
This output has contributed to the advancement of the following goals:
Source: InCites
Abstract
The mechanistic target of rapamycin complex 1 (mTORC1) regulates synaptic protein synthesis and therefore synaptic function and plasticity. A role for mTORC1 has recently been demonstrated for addiction-related behaviors. For example, central or intra-accumbal injections of the mTORC1 inhibitor rapamycin attenuates several indices of cocaine-seeking including progressive ratio (PR) responding and reinstatement. These behavioral effects are associated with decreased mTORC1 activity and synaptic protein translation in the nucleus accumbens (NAC) and point to a possible therapeutic role for rapamycin in the treatment of addiction. Currently, it is unclear whether similar behavioral and biochemical effects can be achieved by administering rapamycin systemically, which represents a more clinically appropriate route of administration. Here, we assessed the effects of repeated, systemic administration of rapamycin (10 mg/kg, i.p.) on PR responding for cocaine. We also assessed whether systemic rapamycin was associated with changes in measures of mTORC1 activity and GluA1 expression in the ventral and dorsal striatum. We report that systemic rapamycin treatment reduced PR breakpoints to levels comparable to intra-NAC rapamycin. Systemic rapamycin treatment also reduced phosphorylated p70S6K and GluA1 AMPARs within the NAC but not dorsal striatum. Thus, systemic administration of rapamycin is as effective at reducing drug seeking behavior and measures of mTORC1 activity compared to direct accumbal application and may therefore represent a possible therapeutic option in the treatment of addiction. Possible caveats of this treatment approach are discussed.
Details
- Title
- Rapamycin reduces motivated responding for cocaine and alters GluA1 expression in the ventral but not dorsal striatum
- Creators
- Morgan H. James - University of Newcastle AustraliaRikki K Quinn - University of Newcastle AustraliaLin Kooi Ong - University of Newcastle AustraliaEmily M. Levi - University of Newcastle AustraliaDoug W. Smith - University of Newcastle AustraliaPhillip W. Dickson - University of Newcastle AustraliaChristopher V. Dayas - University of Newcastle Australia
- Publication Details
- European journal of pharmacology, Vol.784, pp.147-154
- Publisher
- Elsevier
- Grant note
- This work was supported by project grants from the National Health and Medical Research Council (NHMRC) of Australia and an NHMRC CJ Martin Fellowship (1072706) to M.H.J
- Identifiers
- 991013086313202368
- Copyright
- Crown Copyright (C) 2016 Published by Elsevier B.V. All rights reserved.
- Academic Unit
- SCU College
- Language
- English
- Resource Type
- Journal article