Speaker 4: Junghee Lee, USA

s | 39 Abstract Oxytocin has been proposed as a potential treatment approach in drug addiction, but little is known about the effects of oxytocin in translationally relevant models of addiction or the neurobiological substrates of the actions of oxytocin. This presentation highlights the ability of oxytocin to reduce drug taking and drug seeking in a rat model of methamphetamine (meth) addiction. In the first set of experiments, we developed and applied a behavioral economics model of meth addiction to assess the effects of oxytocin on both meth demand and conditioned cueinduced reinstatement of meth seeking following a period of drug withdrawal. Systemic oxytocin treatment reduced both meth demand (determined by an increase in α, the downward acceleration of a demand curve) and reinstatement of cueinduced meth seeking. Notably, oxytocin had the highest efficacy to reduce reinstatement in those rats showing the highest motivation for meth. A second set of experiments examined the central effects of oxytocin on meth demand and reinstatement. The effects of systemic oxytocin on meth demand were completely blocked by central infusion (icv) of an oxytocin receptor antagonist, while direct application of oxytocin in the nucleus accumbens (NAc) abolished the effects of oxytocin on both meth demand and reinstatement. Finally, oxytocin activity in the NAc was found to be necessary for enhanced meth demand, as central antagonism of oxytocin receptors in the NAc blocked the effects of systemic oxytocin. Taken together, these results show a centrally mediated action of oxytocin in reducing demand for meth and cueinduced reinstatement of meth seeking. Future development of oxytocin-based pharmacotherapy may be beneficial for psychostimulant addiction.Oxytocin has been proposed as a potential treatment approach in drug addiction, but little is known about the effects of oxytocin in translationally relevant models of addiction or the neurobiological substrates of the actions of oxytocin. This presentation highlights the ability of oxytocin to reduce drug taking and drug seeking in a rat model of methamphetamine (meth) addiction. In the first set of experiments, we developed and applied a behavioral economics model of meth addiction to assess the effects of oxytocin on both meth demand and conditioned cueinduced reinstatement of meth seeking following a period of drug withdrawal. Systemic oxytocin treatment reduced both meth demand (determined by an increase in α, the downward acceleration of a demand curve) and reinstatement of cueinduced meth seeking. Notably, oxytocin had the highest efficacy to reduce reinstatement in those rats showing the highest motivation for meth. A second set of experiments examined the central effects of oxytocin on meth demand and reinstatement. The effects of systemic oxytocin on meth demand were completely blocked by central infusion (icv) of an oxytocin receptor antagonist, while direct application of oxytocin in the nucleus accumbens (NAc) abolished the effects of oxytocin on both meth demand and reinstatement. Finally, oxytocin activity in the NAc was found to be necessary for enhanced meth demand, as central antagonism of oxytocin receptors in the NAc blocked the effects of systemic oxytocin. Taken together, these results show a centrally mediated action of oxytocin in reducing demand for meth and cueinduced reinstatement of meth seeking. Future development of oxytocin-based pharmacotherapy may be beneficial for psychostimulant addiction.