The role of melatonin in the hippocampus
Specific melatonin binding sites exist in the hippocampus of many species
(Niles 1987; Laudon et al. 1988; Anis et al. 1989; Stankov et al. 1991, 1993;
Deveson et al. 1992; Nonno et al. 1995)
As already mentioned, melatonin can bind to many sites on the plasma
membrane (MT1, MT2, GABAA receptors and K+ channels), and
within the cytoplasm (calmodulin, PKA, PKC, free radicals). Therefore identification of these binding sites as plasma
membrane melatonin receptors has been difficult.
Cloning of melatonin receptor (Fujieda et al. 1999; Oblap and Olszanska
2001; Wiechmann and Smith 2001) has greatly aided in the identification of
melatonin receptors within different tissues
In the vasculature of the human hippocampus specific MT1 mRNA has been
immunohistochemicaly localized (Savaskan et al. 2001).
In hippocampal pyramidal neurons of humans and rodents, MT1 and MT2
receptor mRNA has been found (Mussoff et al. 2002; Savaskan et al. 2001; Wan et
While presence of mRNA for melatonin receptors indicates that the
receptors can be expressed, it does not necessarily indicate that they are
Studies demonstrating actions of melatonin or its analogues on
hippocampal physiology are common (Carnerio and Reiter 1998; El-Sherif et al.
2002; Southgate et al. 1998; Arushanian and Beier 1998; Zamorsjii and Pishak
2000; Won et al. 2000; Ortiz et al. 2001 Hogan et al. 2001; Collins and Davies
In the rodent hippocampus, melatonin has been shown to decrease
hippocampal activity (Hogan et al. 2001; El-Sherif et al. 2001), and block the
induction of LTP (Collins and Davies 1997).
In guinea pig hippocampus, melatonin was shown to lower hippocampal
excitability and paired-pulse facilitation by modulating the membrane potential
(Zeise and Semm 1985). These four
studies all looked at the effects of melatonin in the micromolar range.
As mentioned previously oral consumption of melatonin can significantly
raise levels of melatonin, making these results relevant to the possible effects
of melatonin in humans following melatonin ingestion.
Therefore pursuing our goal of evaluating the influence of melatonin on
the hippocampal neurons, we used a broad range of concentrations of this
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