TY - JOUR
T1 - Hippocampal nAChRs mediate nicotine withdrawal-related learning deficits
AU - Davis, Jennifer A.
AU - Gould, Thomas J.
N1 - Funding Information:
The authors would like to acknowledge grant support from the National Institute on Drug Abuse (DA017949 TG; DA024787 TG). Jennifer A. Davis was supported by a National Institute on Drug Abuse predoctoral fellowship (DA021949). The National Institute on Drug Abuse had no further role in this research.
PY - 2009/8
Y1 - 2009/8
N2 - Nicotine modulation of learning may contribute to its abuse liability. The role of hippocampal nicotinic acetylcholine receptors (nAChRs) in the effects of acute, chronic and withdrawal from chronic nicotine on learning was assessed via intrahippocampal drug infusion in mice. Acute dorsal hippocampal nicotine infusion enhanced contextual fear conditioning. Conversely, chronic intrahippocampal infusion of a matched dose had no effect, and withdrawal from chronic infusion impaired learning. Thus, hippocampal functional adaptation, evidenced by learning deficits during abstinence, occurs with the transition from acute to chronic nicotine exposure. To investigate which hippocampal nAChRs mediate these adaptations, C57BL/6, β2 nAChR subunit knockout (KO), and wildtype (WT) mice treated chronically with systemic nicotine received intrahippocampal dihydro-β-erythroidine (a high affinity nAChR antagonist). Intrahippocampal dihydro-β-erythroidine precipitated learning deficits in all but the KO mice. Therefore, the action of nicotine at hippocampal β2* nAChRs mediates adaptations in hippocampal function that underlie withdrawal deficits in contextual fear conditioning.
AB - Nicotine modulation of learning may contribute to its abuse liability. The role of hippocampal nicotinic acetylcholine receptors (nAChRs) in the effects of acute, chronic and withdrawal from chronic nicotine on learning was assessed via intrahippocampal drug infusion in mice. Acute dorsal hippocampal nicotine infusion enhanced contextual fear conditioning. Conversely, chronic intrahippocampal infusion of a matched dose had no effect, and withdrawal from chronic infusion impaired learning. Thus, hippocampal functional adaptation, evidenced by learning deficits during abstinence, occurs with the transition from acute to chronic nicotine exposure. To investigate which hippocampal nAChRs mediate these adaptations, C57BL/6, β2 nAChR subunit knockout (KO), and wildtype (WT) mice treated chronically with systemic nicotine received intrahippocampal dihydro-β-erythroidine (a high affinity nAChR antagonist). Intrahippocampal dihydro-β-erythroidine precipitated learning deficits in all but the KO mice. Therefore, the action of nicotine at hippocampal β2* nAChRs mediates adaptations in hippocampal function that underlie withdrawal deficits in contextual fear conditioning.
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U2 - 10.1016/j.euroneuro.2009.02.003
DO - 10.1016/j.euroneuro.2009.02.003
M3 - Article
C2 - 19278836
AN - SCOPUS:67549130475
SN - 0924-977X
VL - 19
SP - 551
EP - 561
JO - European Neuropsychopharmacology
JF - European Neuropsychopharmacology
IS - 8
ER -