Methamphetamine-induced changes in the mice hippocampal neuropeptide Y system: implications for memory impairment.
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, Y(1)  and Y(2)  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 Y(5)  receptor mRNA levels, as well as total NPY binding accounted by opposite up- and down-regulation of Y(2)  and Y(1)  functional binding, respectively. Moreover, METH-induced impairment in memory performance and AKT/mammalian target of rapamycin pathway were both prevented by the Y(2)  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.
Laboratory of Pharmacology and Experimental Therapeutics, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
Joana
J
Gonçalves
Sofia
S
Baptista
Mikkel V
MV
Olesen
Carlos
C
Fontes-Ribeiro
João O
JO
Malva
David P
DP
Woldbye
Ana P
AP
Silva
D000818:Animals; D000697:Central Nervous System Stimulants / Q000633:toxicity*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced* / Q000378:metabolism; D008694:Methamphetamine / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D009478:Neuropeptide Y / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
D000697:Central Nervous System Stimulants; D009478:Neuropeptide Y; D017476:Receptors, Neuropeptide Y; C095889:neuropeptide Y2 receptor; D008694:Methamphetamine; C546843:mTOR protein, mouse; C514862:Akt1 protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases