title: Effects of simvastatin and 6-hydroxydopamine on histaminergic H1 receptor binding density in rat brains.
abstract: Statins have been widely used for the treatment of a variety of medical conditions including psychoneurological disorders beyond their original use in lowering cholesterol. Histamine receptors play an important role in the regulation of neural activity, however, it is unknown whether statins act on histamine receptors, particularly for their neural regulatory effects. This study examined the effects of simvastatin and 6-hydroxydopamine (6-OHDA) lesions on histamine H1 receptors using [(3)H] pyrilamine binding autoradiography. Compared to the saline group, simvastatin (1 mg/kg/day) significantly decreased H1 receptor bindings in the primary motor cortex (M1), ventromedial hypothalamic nucleus (VMH), caudate putamen (CPu), accumbens core (AcbC) and prefrontal cortex (PfC) (all p<0.05); however 10 mg/kg/day simvastatin increased H1 receptor density only in the medial amygdaloid nucleus (Mep) (p<0.05), but had no significant effect in other regions examined. The 6-OHDA lesion did not alter H1 receptor binding density in most brain areas, except a trend decrease in the hippocampus (p=0.07) and a trend increase in the cingulate cortex (p=0.06). These results suggested that simvastatin has different effects on the H1 receptors in different rat brain regions depending on the doses. Therefore, simvastatin can modulate histaminergic neurotransmission in the brain, and support the role of H1 receptors in psychoneurological disorders.
authors: Centre for Translational Neuroscience, School of Health Sciences, University of Wollongong, Wollongong, 2522, NSW, Australia.
authors: Chang-Hua
authors: CH
authors: Hu
authors: Chao
authors: C
authors: Deng
authors: Nikolce
authors: N
authors: Mackovski
authors: Ling
authors: L
authors: Long
authors: Cansheng
authors: C
authors: Zhu
authors: Yu
authors: Y
authors: Yang
authors: Yuge
authors: Y
authors: Wang
authors: Jiezhong
authors: J
authors: Chen
authors: Xu-Feng
authors: XF
authors: Huang
authors: Qing
authors: Q
authors: Wang
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D016627:Oxidopamine / Q000633:toxicity*; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011969:Receptors, Histamine H1 / Q000378:metabolism*; D019821:Simvastatin / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D011969:Receptors, Histamine H1; D016627:Oxidopamine; D019821:Simvastatin