78, p < 0.05). In order to sort this, ANOVAs were conducted for Mn for each age and rearing condition. At P11 there were no significant effects of Regorafenib in vivo Mn, rearing condition, or SWS (Fig. 1, top). At P19 for Standard housing, there were both Mn (F(2,198) =3.11, p < 0.05) and Mn x SWS effects (F(6,198) = 3.87, p < 0.01). The Mn main effect was the result of increased corticosterone in the Mn-exposed groups (Fig. 1, middle, left inset). Slice ANOVAs on the interaction showed a Mn effect immediately upon removal from the SWS (time-0)
in which the Mn-exposed groups showed increased corticosterone compared with VEH (Fig. 2, middle-left). At P19 for Barren housing, there was a significant main effect of Mn (F(2,231) = 3.38, p < 0.05), but no interactions. The main effect was attributable to reduced corticosterone in the barren Mn100 group, but note that this was against a higher pre-SWS in the Barren housing groups than in the Standard housing groups (Fig. 1, middle, right inset, andcf.middle, left inset). There was, at this age, a significant SWS main effect (F(3,231) = 15.47,
p < 0.0001). At P29 for both Standard and Barren housing, there were no significant main effects or interactions with Mn. There were main effects of SWS (Standard F(3,198) = 51.44, p < 0.0001; Barren F(3,176) = 50.58, p < 0.0001) ( Fig. 1, bottom). There were no significant effects of Mn or rearing condition on 5-HT in the neostriatum at any age (not shown). For DA, there was a significant Mn × rearing condition × age × sex interaction; (F(4,220) = 2.45, p < 0.05, Fig. 2A-D). Slice and FDR analyses revealed the effect to be in the female Inositol monophosphatase 1 Standard housed Mn100 group (Fig. 2C) at P19 in which the Mn100 SCH772984 in vivo group showed increased DA compared with Standard housed VEH females at this age. No significant treatment effects were found on DOPAC. For neostriatal NE, there were significant Mn (F(2,186) = 9.11, p < 0.001) and Mn × sex × age effects (F(4,186) = 5.3, p < 0.001).
Slice ANOVAs and pairwise comparisons showed the pattern illustrated in Fig. 3 in which there were increases in NE in female Mn50 and Mn100 groups at different ages irrespective of housing condition compared with VEH females. Similarly, there was a Mn main effect on HVA in the neostriatum (F(2,209) = 5.59, p < 0.01: Fig. 4) and a Mn × age × sex interaction (F(4,209) = 3.28, p < 0.05). When the latter effect was further analyzed, the effects occurred in the male Mn50 and Mn100 groups at P19 and in females in the Mn100 group at P29, both irrespective of rearing condition (Fig. 4, panels E and F in which rearing conditions were combined). Monoamine levels in the hippocampus were also affected by Mn and rearing condition (Fig. 5). A significant main effect of Mn (F(2,129) = 3.43, p < 0.05) was evident for DA, such that Mn groups had increased DA compared with VEH (Fig. 5E); the main effect of rearing condition showed a trend toward increased DA across all Barren reared groups F(1,129) = 3.59, p ≤ 0.06).