Ontogenetic Quinpirole Treatments Produce Spatial Memory Deficits and Enhance Skilled Reaching in Adult Rats

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There is a paucity of data on neurochemical abnormalities and associated effects on cognition and motor performance in rats ontogenetically treated with quinpirole, a rodent model of dopaminergic hyperfunction. The objective of the current study was to analyze the cognitive and motor effects produced by ontogenetic administration of quinpirole, a dopamine D2/D3 receptor agonist. Past research from this laboratory has shown that ontogenetic quinpirole treatment sensitizes D2 receptors and produces a variety of characteristic stereotypic behaviors in adult rats. In the current study, rats received quinpirole HCl (1 mg/kg/day) or saline from postnatal day (PD) 1 to PD 11 and went otherwise untreated until adulthood (PD 60). In Experiment 1, cognitive performance was assessed on the standard and matching-to-place versions of the Morris water task (MWT). In Experiment 2, skilled motor performance was assessed on the Whishaw reaching task and locomotor activity was also analyzed. We found that ontogenetically quinpirole-treated rats displayed a deficit on the probe trial given at the end of training of the standard version of the MWT but that there were no significant differences from control on the matching-to-place task. Additionally, rats treated in ontogeny with quinpirole showed significant enhancement in reaching accuracy on the Whishaw reaching task as well as increased locomotor activity relative to saline controls. These findings demonstrate that ontogenetic quinpirole treatments produce cognitive deficits, enhanced skilled reaching and hyperlocomotion. The behavioral changes produced by ontogenetic quinpirole treatment are consistent with dopaminergic hyperfunction, and possible mechanisms are discussed.