Anxiolytic effects of oxytocin in cue-induced cocaine seeking behavior in rats.
BACKGROUND
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.


OBJECTIVE
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.
Department of Pharmacology and Toxicology, University of Puerto Rico-Medical Sciences Campus, P.O. Box 565067, San Juan, PR, 00936, USA, amarilys.morales@gmail.com.
Amarilys
A
Morales-Rivera
Mayté M
MM
Hernández-Burgos
Arlene
A
Martínez-Rivera
Jeremy
J
Pérez-Colón
Raymond
R
Rivera
Janitza
J
Montalvo
Enrique
E
Rodríguez-Borrero
Carmen S
CS
Maldonado-Vlaar
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001007:Anxiety / Q000188:drug therapy*; D001522:Behavior, Animal / Q000187:drug effects*; D003042:Cocaine / Q000008:administration & dosage*; D003463:Cues; D058999:Drug-Seeking Behavior / Q000187:drug effects*; D005108:Extinction, Psychological / Q000187:drug effects; D008297:Male; D010121:Oxytocin / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012646:Self Administration
D014151:Anti-Anxiety Agents; D010121:Oxytocin; D003042:Cocaine