Gestational manganese intoxication and anxiolytic-like effects of diazepam and the 5-HT1A receptor agonist 8-OH-DPAT in male Wistar rats

Abstract

In the present study, the effects of prenatal manganese (Mn) intoxication on the anxiolytic-like effects of diazepam and the 5-HT1A receptor agonist R-(+)-8-hydroxy-dipropylaminotetralin (8-OH-DPAT) were examined. Wistar dams were exposed to MnCl2•4H2O at 5, 000 ppm in the drinking water for the duration of pregnancy. On the day of parturition, Mn was discontinued as an additive in the drinking water. Control rats were derived from dams that consumed tap water and had no exposure to Mn. Male offspring were tested at the age of 12 weeks. The anxiolytic-like effect was assessed in an elevated plus maze device and with the Vogel conflict test. The benzodiazepine anxiolytic diazepam (5mg/kg, ip) increased the percentage of time spent in open arms in control rats (in comparison to saline treatment) (p<0.05); no such effect was seen in Mn-exposed rats. Conversely, the serotoninergic 5-HT1A agonist 8-OH-DPAT (0.3mg/kg, ip) increased the percentage of time spent in open arms in both experimental groups. In the Vogel drinking test, an anxiolytic-like effect was also observed in both test groups (in controls this was of borderline significance). In contrast, 8-OH-DPAT did not evoke an anxiolytic-like action in control or in Mn-exposed rats in the anticonflict test. In conclusion, findings indicate that gestational Mn exposure attenuated benzodiazepine-mediated anxiolytic-like effects but not those of the 5-HT1A receptor agonist 8-OH-DPAT.