Methamphetamine-induced changes in the mice hippocampal neuropeptide Y system: implications for memory impairment.

TY - JOUR

T1 - Methamphetamine-induced changes in the mice hippocampal neuropeptide Y system: implications for memory impairment.

AU - Gonçalves, J

AU - Baptista, S

AU - Olesen, MV

AU - Malva, JO

AU - Woldbye, David Paul Drucker

AU - Silva, AP

PY - 2012/12

Y1 - 2012/12

N2 - Methamphetamine (METH) is a psychostimulant drug that causes irreversible brain damage leading to several neurological and psychiatric abnormalities, including cognitive deficits. Neuropeptide Y (NPY) is abundant in the mammalian central nervous system (CNS) and has several important functions, being involved in learning and memory processing. It has been demonstrated that METH induces significant alteration in mice striatal NPY, Y1 and Y2 receptor mRNA levels. However, the impact of this drug on the hippocampal NPY system and its consequences remain unknown. Thus, in this study, we investigated the effect of METH intoxication on mouse hippocampal NPY levels, NPY receptors function, and memory performance. Results show that METH increased NPY, Y 2 and Y5 receptor mRNA levels, as well as total NPY binding accounted by opposite up- and down-regulation of Y2 and Y1 functional binding, respectively. Moreover, METH-induced impairment in memory performance and AKT/mammalian target of rapamycin pathway were both prevented by the Y2 receptor antagonist, BIIE0246. These findings demonstrate that METH interferes with the hippocampal NPY system, which seems to be associated with memory failure. Overall, we concluded that Y 2 receptors are involved in memory deficits induced by METH intoxication. Involvement of NPY Y2 receptors in METH-induced memory deficit Our main goal was to evaluate the alterations of hippocampal neuropeptide Y (NPY) system induced by methamphetamine (METH) and the possible involvement of these changes in memory deficit induced by the drug. The present work highlights the importance of the hippocampal NPY system, and the functional relationship between Y2 receptors and AKT/mTOR pathway activation in memory impairment induced by METH. Thus, we may suggest that targeting this specific pathway or the modulation of Y2 receptor activity could provide interesting therapeutic approaches.

AB - Methamphetamine (METH) is a psychostimulant drug that causes irreversible brain damage leading to several neurological and psychiatric abnormalities, including cognitive deficits. Neuropeptide Y (NPY) is abundant in the mammalian central nervous system (CNS) and has several important functions, being involved in learning and memory processing. It has been demonstrated that METH induces significant alteration in mice striatal NPY, Y1 and Y2 receptor mRNA levels. However, the impact of this drug on the hippocampal NPY system and its consequences remain unknown. Thus, in this study, we investigated the effect of METH intoxication on mouse hippocampal NPY levels, NPY receptors function, and memory performance. Results show that METH increased NPY, Y 2 and Y5 receptor mRNA levels, as well as total NPY binding accounted by opposite up- and down-regulation of Y2 and Y1 functional binding, respectively. Moreover, METH-induced impairment in memory performance and AKT/mammalian target of rapamycin pathway were both prevented by the Y2 receptor antagonist, BIIE0246. These findings demonstrate that METH interferes with the hippocampal NPY system, which seems to be associated with memory failure. Overall, we concluded that Y 2 receptors are involved in memory deficits induced by METH intoxication. Involvement of NPY Y2 receptors in METH-induced memory deficit Our main goal was to evaluate the alterations of hippocampal neuropeptide Y (NPY) system induced by methamphetamine (METH) and the possible involvement of these changes in memory deficit induced by the drug. The present work highlights the importance of the hippocampal NPY system, and the functional relationship between Y2 receptors and AKT/mTOR pathway activation in memory impairment induced by METH. Thus, we may suggest that targeting this specific pathway or the modulation of Y2 receptor activity could provide interesting therapeutic approaches.

U2 - 10.1111/jnc.12052

DO - 10.1111/jnc.12052

M3 - Journal article

C2 - 23061411

SN - 0022-3042

VL - 123

SP - 1041

EP - 1053

JO - Journal of Neurochemistry

JF - Journal of Neurochemistry

IS - 6

ER -