title: Methylphenidate restores novel object recognition in DARPP-32 knockout mice.
abstract: Previously, we have shown that Dopamine- and cAMP-regulated phosphoprotein of 32kDa (DARPP-32) knockout mice required significantly more trials to reach criterion than wild-type mice in an operant reversal-learning task. The present study was conducted to examine adult male and female DARPP-32 knockout mice and wild-type controls in a novel object recognition test. Wild-type and knockout mice exhibited comparable behavior during the initial exploration trials. As expected, wild-type mice exhibited preferential exploration of the novel object during the substitution test, demonstrating recognition memory. In contrast, knockout mice did not show preferential exploration of the novel object, instead exhibiting an increase in exploration of all objects during the test trial. Given that the removal of DARPP-32 is an intracellular manipulation, it seemed possible to pharmacologically restore some cellular activity and behavior by stimulating dopamine receptors. Therefore, a second experiment was conducted examining the effect of methylphenidate. The results show that methylphenidate increased horizontal activity in both wild-type and knockout mice, though this increase was blunted in knockout mice. Pretreatment with methylphenidate significantly impaired novel object recognition in wild-type mice. In contrast, pretreatment with methylphenidate restored the behavior of DARPP-32 knockout mice to that observed in wild-type mice given saline. These results provide additional evidence for a functional role of DARPP-32 in the mediation of processes underlying learning and memory. These results also indicate that the behavioral deficits in DARPP-32 knockout mice may be restored by the administration of methylphenidate.
authors.affiliation: Department of Neuroscience, University of California, San Diego, La Jolla, CA 92093, USA. cheyser@ucsd.edu
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Heyser
authors.forename: Caitlyn H
authors.initials: CH
authors.lastname: McNaughton
authors.forename: Donna
authors.initials: D
authors.lastname: Vishnevetsky
authors.forename: Allen A
authors.initials: AA
authors.lastname: Fienberg
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003627:Data Interpretation, Statistical; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32 / Q000235:genetics*; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D008297:Male; D008774:Methylphenidate / Q000494:pharmacology*; D051379:Mice; D018345:Mice, Knockout; D011247:Pregnancy; D021641:Recognition, Psychology / Q000187:drug effects*; D012727:Sex Characteristics
chemical_list: D000697:Central Nervous System Stimulants; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; C497929:Ppp1r1b protein, mouse; D008774:Methylphenidate
keywords: DARPP-32; Memory; Methylphenidate; Novel object recognition; Ritalin