Generation and characterization of hD ₅ and C-terminal mutant hD _5m transgenic rats

Dopamine D ₁-like receptors play important roles in many brain activities such as cognition and emotion. We have generated human hD ₅ and mutant human hD ₅ (hD _5m) transgenic rats. The C-terminal juxtamembrane domain of mutant hD ₅ was identical to that of hD5 pseudogenes. The transgenes were driven by the CAMKII promoter that led the expression mainly in the cerebral cortex and hippocampus. We have used different dopamine receptor agonists to compare the pharmacological profiles of the human hD ₅ and hD _5m receptors. The results showed that they exhibited distinct pharmacological properties. Our results of pharmacological studies indicated that the C-terminal of D ₅ receptor could play important roles in agonist binding affinity. Hippocampal long-term potentiation (LTP) evoked by tetanic stimulation was significantly reduced in both transgenic rats. In addition, we found that the overexpression of dopamine hD ₅ and hD _5m receptors in the rat brain resulted in memory impairments. Interestingly, an atypical D ₁-like receptor agonist, SKF83959, could induce anxiety in hD _5m receptor transgenic rats but had no effect on the anxiety-like behavior in D ₅ receptor transgenic and wild-type rats.