Neonatal quinpirole treatment impairs Morris water task performance in early postweanling rats: relationship to increases in corticosterone and decreases in neurotrophic factors.
BACKGROUND
Past studies from this laboratory have shown that quinpirole administration from postnatal day (P) 1-21 produces persistent supersensitization of the dopamine D2 receptor that persists throughout the animal's lifetime.


METHODS
In Experiment 1, both male and female rats were treated with quinpirole or saline from P1-21 and tested on the place and match-to-place versions of the Morris water task (MWT) from P22-28. In Experiment 2, both male and female rats were administered either acute or chronic injections of quinpirole (1 mg/kg) or saline beginning on P1 until analysis for corticosterone (CORT) on P7, 14, or 21.


RESULTS
Neonatal quinpirole treatment produced deficits on both versions of the MWT compared with saline control. One day after behavioral testing, brain tissue was harvested, and the hippocampus was analyzed for nerve growth factor (NGF) and brain-derived nerve growth factor (BDNF); NGF was found to be significantly decreased by neonatal quinpirole treatment. Acute or chronic quinpirole treatment on P14 produced a larger increase in CORT than controls and produced larger increases in CORT than control rats on P21.


CONCLUSIONS
These results demonstrate that neonatal quinpirole treatment produces cognitive deficits that could be related to decreases in hippocampal NGF and increases in CORT, resulting in abnormalities in hippocampal development.
Department of Psychology, Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee, USA. brown@mail.etsu.edu
Russell W
RW
Brown
Timothy J
TJ
Flanigan
Kimberly N
KN
Thompson
Stephanie K
SK
Thacker
Tori L
TL
Schaefer
Michael T
MT
Williams
D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000187:drug effects*; D003345:Corticosterone / Q000378:metabolism*; D018491:Dopamine Agonists / Q000494:pharmacology*; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects*; D009414:Nerve Growth Factors / Q000378:metabolism*; D019257:Quinpirole / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D012737:Sex Factors
D018491:Dopamine Agonists; D009414:Nerve Growth Factors; D019257:Quinpirole; D003345:Corticosterone