Abstract
Rationale
Oxytocin (OT) is a neuropeptide previously related to reward, learning, memory, and stress, events associated with cocaine addiction. OT has shown anxiolytic properties in different animal models of anxiety. Moreover, previous data have demonstrated an increase in mRNA OT levels within the nucleus accumbens (NAc) following acute and chronic cocaine exposure in rats. Therefore, OT might play a modulatory role in the rewarding properties of cocaine.
Objectives
The present set of experiments aims to examine the role of OT on environmentally elicited cocaine-seeking behavior and whether OT could reduce anxiety associated with this behavior.
Methods
Separate groups of rats were trained in a cue-elicited cocaine-seeking behavior paradigm. Prior to the reinstatement phase, animals received microinfusions of artificial cerebrospinal fluid (aCSF), OT, OT agonist (TgOT), or OT antagonist (OTA) within the intracerebral ventricular intracerebroventricular (ICV) system. To test OT anxiolytic effects in reinstatement behavior, separate groups of animals were trained in a cue-elicited cocaine-seeking behavior protocol or in a cocaine-conditioning paradigm. At the end of each behavioral training, all animals were ICV pretreated with aCSF or OT, and then exposed to an elevated plus maze.
Results
Results showed that OT and TgOT pretreatment significantly reduced reinstatement of cocaine-seeking behavior. Most significantly, OT treatment reduced the anxiety triggered by cue-induced reinstatement conditions and cocaine-paired conditioned locomotion.
Conclusions
The present study demonstrates for the first time that OT actions within the brain mediate the anxiety response triggered by cues previously paired with cocaine intake.
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Abbreviations
- aCSF:
-
Artificial cerebral spinal fluid
- DA:
-
Dopamine
- FR1:
-
Fixed ratio 1
- FR5:
-
Fixed ratio 5
- FR10:
-
Fixed ratio 10
- HPA:
-
Hypothalamus pituitary axis
- NAc:
-
Nucleus accumbens
- OT:
-
Oxytocin
- OTA:
-
Oxytocin antagonist
- PFC:
-
Prefrontal cortex
- TgOT:
-
[Thr4,Gly7]-oxytocin/oxytocin agonist
- VTA:
-
Ventral tegmental area
- TO:
-
timeout
- AD:
-
Ambulatory distance
- EPM:
-
Elevated plus maze
- CeL:
-
Lateral central amygdala
- CeA:
-
Central amygdala
- CeM:
-
Central medial amygdala
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Acknowledgments
The authors would like to thank Dr. Maurice Manning for providing the TgOT. The authors would also like to thank Raysa López, Nadya Rivera, and Siomara Molina for their technical support and Dr. Cornelis P. Vlaar for his insightful comments on the writing of this manuscript. This research was supported by SCORE S06GM 5S06M08102 (CSMV), MBRS-RISE R25-GM061838 (AMR), and NIH-MARC grant no. 5T34GM07821-32 (MMHB). Research reported in this publication was supported by the National Institute of General Medical Sciences. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
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Morales-Rivera, A., Hernández-Burgos, M.M., Martínez-Rivera, A. et al. Anxiolytic effects of oxytocin in cue-induced cocaine seeking behavior in rats. Psychopharmacology 231, 4145–4155 (2014). https://doi.org/10.1007/s00213-014-3553-y
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DOI: https://doi.org/10.1007/s00213-014-3553-y