Somatotropin (GH) and insulin (INS) low dose, long-term brain rejuvenation effect was studied in the cerebral cortex using NE, EPI, DA and 5-HT receptor subtypes of young (group I-treatment started 4 weeks continued to 16 weeks) and old rats (group II-treatment started 60 weeks continued to 90 weeks). GH and INS treatment showed significant decrease in NE and EPI content in cerebral cortex of both young and old rats. alpha(2A)-adrenergic receptors showed decreased expression whereas beta(2)-adrenergic receptors showed enhanced expression with age. GH and INS treatment significantly increased alpha(2A)-adrenergic receptor protein in group I rats whereas INS treatment could increase beta(2)-adrenergic receptor protein expression in group II rats. DA and 5-HT content decrease with age. GH and INS administration showed increase in DA and 5-HT content in the brain regions-corpus striatum and brainstem of both young and old rats. Also, DA D(2) and 5-HT(2C) receptor gene expression were increased significantly by GH and INS treatment in both young and old rats. In conclusion, low dose, long-term treatment of INS and GH to ageing rats improved the adrenergic, dopaminergic and serotonergic receptor subtypes activity and rejuvenation of brain function.