.. Hebbian-type plasticity is involved during methamphetamine induced

CPP We report for the first time that METH applied into the VTA of the midbrain using a reverse microdialysis technique induces VE-821 in vitro positive CPP. We also for the first time showed that the place reinforcement induction capacity of METH is dependent on the hippocampal-VTA loop. We observed that conditioning the bottom-up pathway of this loop, in the order of VTA first, followed by VHC, and finally NAc, produced positive place preference learning irrespective Inhibitors,research,lifescience,medical of where in the aforementioned three brain nuclei to which the drug was applied (Figs. 3, ​,4,4, and ​and5).5). In contrast, conditioning the top-down pathway of this Inhibitors,research,lifescience,medical loop, which involves earlier activation of the VHC using METH in the order of VHC, followed by VTA, and finally NAc, attenuated METH-induced positive CPP and thereby produced a place aversion (Figs. 6, ​,7,7, and ​and8).8). The aversive effects of METH in the top-down order of conditioning Inhibitors,research,lifescience,medical were attenuated by coadministration of METH with the NMDA receptor noncompetitive antagonist MK801 (in 1:1 ratio). This observation overall implies that there exists a Hebbian-type

synaptic plasticity in which earlier activation of either of the two pathways in the hippocampus-VTA loop dominates and hence gradually produces an all-or-none plasticity; a plasticity of either positive place reinforcement learning (the bottom-up pathway) or plasticity of place aversion (the top-down pathway). There might be a dorsoventral distinction Inhibitors,research,lifescience,medical of the hippocampal formation with respect to reinforcement learning Our laboratory previously reported that amphetamine reverse-dialyzed intra-NAc produced Inhibitors,research,lifescience,medical positive CPP (Rodriguez 2008). In addition, using intrahippocampal METH self administration and

intrahippocampal METH CPP behavioral paradigms, our laboratory reported that METH microdialyzed into the dorsal hippocampus-induced positive reinforcement learning. Ricoy and Martinez, 2009 (Ricoy and Martinez 2009) further reported that the positive reinforcement capacities of METH treatment within the dorsal hippocampus was a D1-like receptor-mediated process because the D1 receptor antagonist Schering, SCH23390, coadministered with METH attenuated the reinforcing efficacy of METH Adenosine (Ricoy and Martinez 2009). However, other research shows that there is a dorsoventral functional segregation of the hippocampal structure in which the dorsal portion performs primarily motor-related cognitive functions, whereas the ventral portion mediates affective behaviors and emotions (Fanselow and Dong 0000). Unlike the case for dorsal hippocampus, our current findings following conditioning the hippocampus-VTA loop was an “if… then…” condition.