Oxytocin reduces cocaine seeking and reverses chronic cocaine-induced changes in glutamate receptor function.
Bottom Line: Immunoprecipitation of oxytocin receptor and GluA1 subunit receptors further demonstrated a physical interaction between these 2 receptors, although the interaction was not influenced by chronic cocaine or oxytocin treatment.Oxytocin also attenuated sucrose seeking in a GluA1- or extracellular-signal-regulated kinase-independent manner.These findings suggest that oxytocin mediates cocaine seeking through interacting with glutamate receptor systems via second messenger cascades in mesocorticolimbic regions.
Affiliation: Department of Neurosciences, Medical University of South Carolina, Charleston, South Carolina (Drs Zhou, Sun, Young, Lee, McGinty, and See).Show MeSH
Related in: MedlinePlus
Mentions: We further explored the impact of OT on responding for cocaine using higher demand schedules of reinforcement. We used a 1-mg/kg dose of OT, as it decreased cocaine seeking on the FR1 schedule of reinforcement (results from experiment 1) without affecting locomotor activity (L. Zhou, PhD, unpublished data, January, 2013). Another set of rats experienced 4 cocaine self-administration sessions on an FR1 schedule of reinforcement followed by 9 sessions using an FR5 schedule. Thirty minutes prior to the fifth and eighth sessions, rats received either vehicle or OT in a counterbalanced order. Rats then underwent 9 daily self-administration sessions on a PR schedule, during which reinforcement was contingent upon an increasing number of responses that incrementally increased through the following equation: Response ratio=(5e[injection number×0.2])−5 (Richardson and Roberts, 1996). Rats were pretreated with vehicle or OT in a counterbalanced order 30 minutes prior to the fifth and eighth sessions. The PR sessions were 5 hours long but were terminated earlier if the rat failed to receive an infusion within 1 hour. A time line for experiment 1 is shown in Figure 1.
Affiliation: Department of Neurosciences, Medical University of South Carolina, Charleston, South Carolina (Drs Zhou, Sun, Young, Lee, McGinty, and See).