RespireRx Pharmaceuticals Inc (RSPI)

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Oxytocin is also being studied as a treatment for drug addiction, and it appears to also function via its effect on AMPA/glutamate pathways (increased phosphorylation of AMPA receptors), as Ampakines do -



http://www.ncbi.nlm.nih.gov/pubmed/25539504




>>> Int J Neuropsychopharmacol. 2014 Oct 31;18(1). pii: pyu009. doi: 10.1093/ijnp/pyu009.

Oxytocin reduces cocaine seeking and reverses chronic cocaine-induced changes in glutamate receptor function.

Zhou L1, Sun WL1, Young AB1, Lee K1, McGinty JF1, See RE2.



Abstract

BACKGROUND:

Oxytocin, a neurohypophyseal neuropeptide, is a potential mediator and regulator of drug addiction. However, the cellular mechanisms of oxytocin in drug seeking remain unknown.

METHODS:

In the present study, we used a self-administration/reinstatement model to study the effects of oxytocin on cocaine seeking and its potential interaction with glutamate function at the receptor level.

RESULTS:

Systemic oxytocin dose-dependently reduced cocaine self-administration during various schedules of reinforcement, including fixed ratio 1, fixed ratio 5, and progressive ratio. Oxytocin also attenuated reinstatement to cocaine seeking induced by cocaine prime or conditioned cues. Western-blot analysis indicated that oxytocin increased phosphorylation of the a-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. 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.

CONCLUSIONS:

These findings suggest that oxytocin mediates cocaine seeking through interacting with glutamate receptor systems via second messenger cascades in mesocorticolimbic regions.

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