Hippocampal leptin suppresses methamphetamine-induced hyperlocomotion.
Leptin is an anorexigenic peptide which is synthesized in white adipose tissue. The actions of leptin are mediated by the leptin receptor which is abundantly localized in the hypothalamus and is involved in energy regulation and balance. Recently, there has been evidence suggesting that the leptin receptor is also present in the hippocampus and may be involved with hippocampal excitability and long-term depression. To investigate the physiological function of leptin signalling in the hippocampus, we studied the effects of leptin on methamphetamine-induced ambulatory hyperactivity by utilizing intra-hippocampal infusion (i.h.) in mice. Our results show that the infusion of leptin (5 ng each bilaterally i.h.) does not affect the basal ambulatory activity but significantly suppresses methamphetamine-induced ambulatory hyperactivity as compared to saline-infused controls. Interestingly, higher dose of leptin increases the suppression of the methamphetamine-induced ambulatory hyperactivity. The i.h. infusion of leptin did not activate the JAK-STAT pathway, which is the cellular signalling pathway through which leptin acts in the hypothalamus. The infusion of leptin also did not affect activation of p42/44 MAPK which is known to be another leptin-induced signalling pathway in the brain. These results demonstrate that leptin has a novel potential suppressive effect on methamphetamine-induced hyperlocomotion and also suggest that there must be an alternative pathway in the hippocampus through which leptin signalling is being mediated.
Nishio
Masahiro
M
Department of Pharmacology, National Defense Medical College, Namiki, Tokorozawa, Japan.
Watanabe
Yasuhiro
Y
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D006948:Hyperkinesis / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D053612:Janus Kinases / Q000502:physiology; D020738:Leptin / Q000494:pharmacology / Q000502:physiology*; D008694:Methamphetamine; D051379:Mice; D008815:Mice, Inbred Strains; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D054411:Receptors, Leptin / Q000502:physiology; D050791:STAT Transcription Factors / Q000502:physiology; D015398:Signal Transduction
D020738:Leptin; D054411:Receptors, Leptin; D050791:STAT Transcription Factors; D008694:Methamphetamine; D053612:Janus Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3