title: Adulthood olanzapine treatment fails to alleviate decreases of ChAT and BDNF RNA expression in rats quinpirole-primed as neonates.
abstract: Neonatal quinpirole (dopamine D(2)/D(3) agonist) treatment to rats has been shown to increase dopamine D(2) receptor sensitivity throughout the animal's lifetime. Male and female Sprague-Dawley rats were neonatalally treated with quinpirole (1 mg/kg) from postnatal days (P) 1-21 and raised to adulthood. Beginning on P62, rats were administered the atypical antipsychotic olanzapine (2.5 mg/kg) twice daily for 28 days. Starting 1 day after the end of olanzapine treatment, animals were behaviorally tested on the place and match-to-place version of the Morris water maze (MWM) over seven consecutive days, and a yawning behavioral test was also performed to test for sensitivity of the D(2) receptor 1 day following MWM testing. Similar to results from a past study, olanzapine alleviated cognitive impairment on the MWM place version and increases in yawning produced by neonatal quinpirole treatment. Brain tissue analyses showed that neonatal quinpirole treatment resulted in a significant decrease of hipppocampal ChAT and BDNF RNA expression that were unaffected by adulthood olanzapine treatment, although adulthood olanzapine treatment produced a significant increase in cerebellar ChAT RNA expression. There were no significant effects of drug treatment on NGF RNA expression in any brain area. These results show that neonatal quinpirole treatment produced significant decreases of protein RNA expression that is specific to the hippocampus. Although olanzapine alleviated cognitive deficits produced by neonatal quinpirole treatment, it did not affect expression of proteins known to be important in cognitive performance.
authors.affiliation: Department of Psychology, East Tennessee State University, Johnson City, TN 37614, USA. brown1@mail.etsu.edu
authors.forename: Russell W
authors.initials: RW
authors.lastname: Brown
authors.forename: Marla K
authors.initials: MK
authors.lastname: Perna
authors.forename: Amanda M
authors.initials: AM
authors.lastname: Maple
authors.forename: Tracy D
authors.initials: TD
authors.lastname: Wilson
authors.forename: Barney E
authors.initials: BE
authors.lastname: Miller
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000375:Aging / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D014150:Antipsychotic Agents / Q000494:pharmacology; D001569:Benzodiazepines / Q000494:pharmacology*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D002795:Choline O-Acetyltransferase / Q000235:genetics*; D003071:Cognition / Q000187:drug effects / Q000502:physiology; D003072:Cognition Disorders / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology; D018491:Dopamine Agonists / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D005260:Female; D006624:Hippocampus / Q000187:drug effects* / Q000254:growth & development* / Q000378:metabolism; D007859:Learning Disabilities / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D000077152:Olanzapine; D019257:Quinpirole / Q000494:pharmacology*; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000378:metabolism; D013995:Time
chemical_list: D014150:Antipsychotic Agents; D019208:Brain-Derived Neurotrophic Factor; D018491:Dopamine Agonists; D012333:RNA, Messenger; D017448:Receptors, Dopamine D2; D001569:Benzodiazepines; D019257:Quinpirole; D002795:Choline O-Acetyltransferase; D000077152:Olanzapine; D000109:Acetylcholine