PT - JOURNAL ARTICLE AU - Sara B. Glickstein AU - Patrick R. Hof AU - Claudia Schmauss TI - Mice Lacking Dopamine D<sub>2</sub> and D<sub>3</sub> Receptors Have Spatial Working Memory Deficits AID - 10.1523/JNEUROSCI.22-13-05619.2002 DP - 2002 Jul 01 TA - The Journal of Neuroscience PG - 5619--5629 VI - 22 IP - 13 4099 - http://www.jneurosci.org/content/22/13/5619.short 4100 - http://www.jneurosci.org/content/22/13/5619.full SO - J. Neurosci.2002 Jul 01; 22 AB - Mice deficient for dopamine D2 and D3receptors exhibit blunted c-fos responses to D1 agonist stimulation. Stereologic cell counting revealed decreased numbers of medial prefrontal cortex neurons that express Fos immunoreactivity in all layers, particularly in the prelimbic and anterior cingulate subregions. Pretreatment of these mutants with a single, low dose of methamphetamine (METH) led to a sustained increase in the number of neurons that express Fos immunoreactivity in response to a D1 agonist challenge, which was most significant in prelimbic and anterior cingulate subregions. The increased c-fos responses reached wild-type-like levels in METH-pretreated D2 mutants but remained submaximal in METH-pretreated D3 mutants. Additional studies tested the performance of wild type and mutants in a delayed alternation test, a cognitive task critically dependent on optimal activation of prefrontal cortical D1 receptors by synaptically released dopamine. Both D2 and D3 mutants exhibited deficits in their spatial working memory, with increasing impairments at increasing delays. Whereas METH pretreatment rescued the spatial working memory of D2 mutants, it had no effect on D3 mutants. These data suggest that the sustained improvement of spatial working memory in METH-pretreated D2 mutants is attributable to D1 receptor-mediated mechanisms.