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Melatonin plays a key role in a variety of important physiological functions including influencing cerebral blood vessels. Therefore, in the present study, we have identified the existence of melatonin receptors and test the effect of melatonin on hydrogen peroxide-induced endothelial nitric oxide synthase (eNOS) expression in bovine cerebral arteries. The results indicate that mt1A melatonin receptor mRNA is expressed in bovine cerebral arteries. The relative levels of mt1A melatonin receptor mRNA expression in anterior, posterior, middle and vertebral cerebral arteries were compared. The data show the highest and lowest levels of mRNA expressions in the middle and vertebral cerebral arteries, respectively. The maximal number (B(max)) of different types of melatonin receptors in various regions of cerebral arteries were identified and further characterized by using the selective 2-[(125)I] iodomelatonin binding assay. Saturation studies revealed that the binding represented a single site of high affinity binding for the melatonin receptor with the highest and lowest binding capacities in the middle and vertebral arteries, respectively. In order to elaborate the functional significance of melatonin in cerebral blood vessels, hydrogen peroxide- induced induction in eNOS protein level and phosphorylation of calcium/calmodulain-dependent protein kinase II (phospho-CaMKII) were demonstrated in the bovine isolated cerebral arteries with these effect being abolished by melatonin. This is the first evidence showing expression of mt1A melatonin receptor in the bovine cerebral arteries. However, further studies are necessary to delineate the role of melatonin and its receptors in regulating physiology of the cerebral vessels.

Background: Methamphetamine (METH) dependence becomes the major public health concern for many countries. METH is an abusive stimulant with various psychophysiological effects to its abusers. METH activates the human&#39;s brain reward circuitry and addiction, by increasing dopamine (DA) and serotonin (5-HT) levels in the synaptic cleft. </P><P> Objective: We investigated allelic variants of 5-HTTLPR, 5-HT1A C(-1019)G, 5-HT2A (102 T/C), and DRD2 Taq IA gene polymorphisms. </P><P> Methods: Subjects were recruited and met the DSM-IV criteria of METH dependence. They were screened with Diagnostic Interview for Genetic Study (DIGS), Family Interview for Genetic Study (FIGS), and a short research questionnaire. Blood samples were collected, and DNA was extracted from leukocytes and PCR-amplified. The PCR products were then digested with enzymes: Hpy CH4IV, MspI, and Taq I restriction enzyme, respectively for 5-HT1A C(-1019)G, 5-HT2A (102 T/C), and DRD2 Taq IA. The genotypes were assigned on agarose gel size fractionation and allele identification. </P><P> Results: The results indicated that METH-dependent patients were likely to be poly-substance abusers. Genetic results showed that there were no differences between genetic variation of 5-HTTLPR, 5-HT1A C(-1019)G, and DRD2 Taq IA gene polymorphisms and METH dependence. For 5-HT2A 102T/C, T/C genotype was found to be significantly higher in METHdependent patients compared to healthy controls. Additionally, there was a significant difference for T allele of 5-HT2A 102T/C in METH-dependent patients with comorbidity of three prominent psychotic features: METH-induced psychosis, suicidal behaviors, and depressive symptoms. </P><P> Conclusion: These results suggest that the METH dependence, psychiatric comorbidity, and genetic variation can pose a challenge in the treatment of METH-dependent patients.