Role of histamine in short- and long-term effects of methamphetamine on the developing mouse brain.
With the rise in methamphetamine (MA) use among women of childbearing age, the potential consequences of MA exposure to the developing brain for cognition in adulthood is a major concern. Histamine might mediate these MA effects. Following MA administration in neonatal mice, histamine levels in brain were elevated and the hypothalamic-pituitary-adrenal axis was activated. Co-administration of MA with the H3 receptor agonist immepip antagonized these effects. The effects of MA on histamine levels and on hypothalamic-pituitary-adrenal axis activation at P20 were more pronounced in female than male mice. These sex differences could have contributed to the increased susceptibility of female mice to the detrimental long-term cognitive effects of MA and the H3/H4 antagonist thioperamide. Following behavioral testing, mice neonatally treated with MA or thioperamide showed reduced levels of the dendritic marker microtubule-associated protein 2 in the CA3 region of the hippocampus and the enthorhinal cortex. This was not seen in mice neonatally treated with immepip and MA who did not show cognitive impairments, suggesting that these brain areas might be particularly important for the long-term effects of MA on cognitive function. These data support a role for histamine in the effects of MA on the developing brain.
Acevedo
Summer F
SF
Department of Behavioral Neuroscience, Oregon Health and Science University, Portland, Oregon 97239, USA.
Pfankuch
Timothy
T
van Meer
Peter
P
Raber
Jacob
J
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000033:anatomy & histology / Q000187:drug effects* / Q000254:growth & development*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003345:Corticosterone / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006632:Histamine / Q000378:metabolism*; D054828:Histamine H3 Antagonists / Q000494:pharmacology; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D008694:Methamphetamine / Q000097:blood / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology; D010913:Pituitary-Adrenal System / Q000187:drug effects; D012737:Sex Factors; D013997:Time Factors
D000697:Central Nervous System Stimulants; D054828:Histamine H3 Antagonists; D007093:Imidazoles; D008869:Microtubule-Associated Proteins; C079240:Mtap2 protein, mouse; D010880:Piperidines; C085755:4-(1H-imidazol-4-ylmethyl)piperidine; D008694:Methamphetamine; D006632:Histamine; C052075:thioperamide; D003345:Corticosterone
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