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Adulthood nicotine treatment alleviates behavioural impairments in rats neonatally treated with quinpirole: possible roles of acetylcholine function and neurotrophic factor expression
Author(s) -
Brown Russell W.,
Thompson Kenyatta D.,
Thompson Kimberly N.,
Ward J. Jeffrey,
Thacker Stephanie K.,
Williams Michael T.,
Kostrzewa Richard M.
Publication year - 2004
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2004.03199.x
Subject(s) - quinpirole , nicotine , endocrinology , medicine , agonist , hippocampus , brain derived neurotrophic factor , psychology , dopamine , cholinergic , hippocampal formation , neurotrophic factors , saline , dopamine receptor d2 , receptor
Abstract Increases in dopamine D 2 receptor sensitivity are known to be common in drug abuse and neurological disorders. Past data from this laboratory have shown that long‐term increases in D 2 sensitivity can be produced by quinpirole treatment (a D 2 /D 3 agonist) during early development. The present investigation was designed to test the hypothesis that nicotine administration in adulthood would reduce both cognitive and skilled reaching impairments produced by increases in D 2 sensitivity. Female Sprague–Dawley rats were treated with quinpirole (1 mg/kg) or saline from postnatal day 1 (PD 1) to PD 21. Beginning in adulthood (PD 61), rats were treated with nicotine (0.3 mg/kg free base) or saline twice daily for 14 consecutive days before behavioural testing commenced. Animals neonatally treated with quinpirole demonstrated performance deficits on the Morris water task and a skilled reaching task compared to controls. Deficits on both tasks were completely alleviated by adulthood nicotine treatment. Animals neonatally treated with quinpirole demonstrated a significant 36% decrease of ChAT in the hippocampus compared to saline controls that was partially eliminated by nicotine. Additionally, neonatal quinpirole produced a significant decrease in hippocampal NGF content compared to controls, however, nicotine failed to alleviate this decrease in NGF. The results of this investigation demonstrate that long‐term increases in dopamine D 2 receptor sensitivity produce significant decreases in hippocampal cholinergic and NGF expression that may result in cognitive impairment. Nicotine alleviates both cognitive and skilled reaching impairments caused by increases in D 2 sensitivity, but the mechanism through which nicotine is acting is currently unknown.