Effect of Methamphetamine on Cognition and Repetitive Motor Behavior of Mice Deficient for Dopamine D2 and D3 Receptors
Mice deficient for dopamine D2 and D3 receptors exhibit blunted D1-receptor responses to agonist stimulation. This blunted D1-receptor activity is prominent in the medial prefrontal cortex (mPFC) and results in a significantly impaired performance of the mutants in a test for spatial working memory. A single dose of methamphetamine (METH; 5 mg/kg i.p.), however, elicits a long-lasting increase in agonist-stimulated D1 receptor activity in the mPFC. In D2 mutants, this increase reaches wild-type levels, and the working memory of METH-treated mutants is completely rescued. In D3 mutants, however, the METH-induced increase in D1-receptor activity remains below wild-type levels and does not result in improved working memory performance.
methamphetamine working memory d1 receptors d2 knockout d3 knockout stereotypy