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Appalachian Student Research Forum

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Division III

Abstracts Submitted:Division III - Graduate students (2 + years) - Social & Behavioral Sciences


CHRONIC OLANZAPINE TREATMENT ELIMINATES COGNITIVE DEFICITS PRODUCED BY D2 RECEPTOR SUPERSENSITIZATION.

Thacker, S. K.; Perna, M. K.; Smith, K. S.; Kostrzewa, R. M.; Brown, R. W. Department of Psychology, East Tennessee State University, Johnson City, TN 37614 USA.

Olanzapine is an effective antipsychotic used to treat schizophrenia. We have developed a rodent model of psychosis through neonatal administration of quinpirole (D2 agonist) that produces long-term D2 receptor supersensitization. Rats were given quinpirole (1mg/kg) or saline treatment from P1-21. Beginning on P61, rats were administered olanzapine (2.5 mg/kg) or saline twice daily (i.p.) for 28 days. Beginning on P90, rats were tested on the place version of the Morris water task (MWT) for three consecutive days. A probe trial, with platform removed, was given at the end of training. The next day, animals began testing on the match-to-place version for four consecutive days and two daily trials were given with the platform moved to a new location each day. On the search time of the probe trial with a two-way ANOVA revealed significant main effects of neonatal drug treatment F(1,36)=4.4, p<.04; adult drug treatment F(1,36)=3.5, p<.04, and the Neonatal x Adulthood drug treatment interaction approached significance (p=.06). On target visits of the probe trial, the Neonatal x Adulthood drug treatment interaction was significant F(1,36)=5.52, p<.02. On both measures, neonatal quinpirole treatment produced cognitive deficits that were eliminated by adulthood olanzapine treatment. On the match-to-place version, the difference in latency to locate the platform between the two daily trials served as the dependent measure. The Neonatal x Adulthood drug treatment interaction was significant F(1,36)=8.5, p<.006. Similar to the place version, olanzapine treatment eliminated deficits produced by neonatal quinpirole treatment on this task. Analyses for neurotrophic factors and choline acetyltransferase in the hippocampus, frontal cortex, and frontal cortex are currently underway. Possibly the most important finding was that chronic olanzapine reversed dopamine D2 supersensitization-induced yawning and chewing behavior on P98 after behavioral testing was complete. This result demonstrates that dopamine D2 supersensitization is responsible for the cognitive impairments in this model.


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