CHMA1004

Wistar rats (male and female; 3 months old at study start; male body weight 499 g, female body weight 290 g)^[1]

1 mg/kg (subchronic; acute microdialysis); 5 mg/kg (subchronic; acute microdialysis)

i.p.; daily; 17-18 days (subchronic); i.p.; single dose (acute microdialysis)

Increased time spent moving, line crossings, and rearings in female rats in acute open field test.
Showed a similar non-significant tendency in males at 5 mg/kg in acute open field test.
Reduced faecal boli counts in male rats at 5 mg/kg in acute open field test.
Increased head-dips in female rats during the first repeated elevated zero-maze test at 1 mg/kg and 5 mg/kg.
Increased open quadrant entries in male rats during the second repeated elevated zero-maze test at 5 mg/kg.
Reduced stretched-attend postures in male rats during the first repeated elevated zero-maze test at 5 mg/kg.
Increased swimming time and reduced struggling time in female rats on both test days of repeated forced swimming test at 1 mg/kg and 5 mg/kg.
Tended to increase locomotion in male rats during amphetamine challenge at subchronic 5 mg/kg.
Reduced the baseline sex difference in 50-kHz USVs by increasing vocalisations in males and reducing them in females during amphetamine challenge at subchronic 5 mg/kg.
Had no significant effect on extracellular striatal dopamine levels in acute microdialysis at 1 mg/kg and 5 mg/kg.
Increased normetanephrine (NMN) levels in males and females in striatum at subchronic 5 mg/kg.
Increased the DOPAC/DA ratio in males in striatum at subchronic 5 mg/kg.
Decreased the DOPAC/DA ratio in females in striatum at subchronic 1 mg/kg.
Increased NMN levels in males in frontal cortex at subchronic 1 mg/kg and 5 mg/kg.
Increased noradrenaline (NA) levels in males in frontal cortex at subchronic 5 mg/kg.
Increased homovanillic acid (HVA) levels in males in locus coeruleus at subchronic 1 mg/kg.
Decreased HVA levels in females in locus coeruleus at subchronic 1 mg/kg and 5 mg/kg.
Increased NA levels in males and females in ventral tegmental area at subchronic 1 mg/kg.
Altered expression of 172 genes (e.g., downregulated Acsm5, Gpr83; upregulated Fgr, Hes1) in striatum of females at subchronic 1 mg/kg.
Altered expression of 120 genes (e.g., downregulated Vwa5b2, Peli1; upregulated Nbl1, Mdga1) in striatum of females at subchronic 5 mg/kg.
Showed consistent expression changes across doses in seven overlapping genes (Galns, Hps3, Misp3, Nbl1, Samd4a, Slc28a2, Spon2) in striatum of females.