Oxytocin reduces cocaine seeking and reverses chronic cocaine-induced changes in glutamate receptor function.
Bottom Line: However, the cellular mechanisms of oxytocin in drug seeking remain unknown.Western-blot analysis indicated that oxytocin increased phosphorylation of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-type glutamate receptor GluA1 subunit at the Ser 845 site with or without accompanying increases in phosphorylation of extracellular signal-regulated kinase, in several brain regions, including the prefrontal cortex, bed nucleus of the stria terminalis, amygdala, and dorsal hippocampus.Oxytocin also attenuated sucrose seeking in a GluA1- or extracellular-signal-regulated kinase-independent manner.
Affiliation: Department of Neurosciences, Medical University of South Carolina, Charleston, South Carolina (Drs Zhou, Sun, Young, Lee, McGinty, and See).Show MeSH
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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on the FR1 schedule of reinforcement (results from experiment 1) without affecting locomotor activity (L. Zhou, PhD, unpublished data, January, 2013).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).