PMID- 18456310
OWN - NLM
STAT- MEDLINE
DCOM- 20080825
LR  - 20220318
IS  - 0091-3057 (Print)
IS  - 0091-3057 (Linking)
VI  - 90
IP  - 3
DP  - 2008 Sep
TI  - Idazoxan blocks the nicotine-induced reversal of the memory impairment caused by 
      the NMDA glutamate receptor antagonist dizocilpine.
PG  - 372-81
LID - 10.1016/j.pbb.2008.03.011 [doi]
AB  - RATIONALE: Alpha2-adrenoreceptor (alpha(2)-AR) antagonists have been shown to 
      improve, while alpha(2)-AR agonists impair cognitive function in subjects with 
      functioning NMDA receptors (NMDAR). In subjects with inhibited NMDAR (a model of 
      schizophrenia) alpha(2)-AR agonists attenuate the cognitive impairments. The 
      effect with alpha(2)-AR antagonists remains unclear. OBJECTIVES: We investigated 
      the effects of the alpha(2)-AR antagonist idazoxan on memory function in rats 
      treated/not treated with NMDAR antagonist dizocilpine or a combination of 
      dizocilpine and nicotine to clarify noradrenergic/cholinergic regulation of 
      memory function. METHODS: Female Sprague-Dawley rats (n=12) were trained for food 
      reward on the radial maze. Working and reference memory errors and response 
      latency were assessed after injections of idazoxan (0.5, 1.0 mg/kg), dizocilpine 
      (0.05 mg/kg), nicotine (0.2, 0.4 mg/kg) or vehicle, alone or in combination. 
      RESULTS: Dizocilpine potently impaired memory. Nicotine (0.4 mg/kg) reversed this 
      impairment. Idazoxan at the doses tested did not affect performance when given 
      alone or with dizocilpine, but it did block the nicotine reversal of the 
      dizocilpine-induced memory impairment. Three rats after 10-12 drug treatments 
      developed limbic seizures. Our findings suggest that combination of drugs which 
      block alpha(2)-AR with nicotinic agonists in schizophrenia may prevent 
      therapeutic effect of nicotinic agonists and increase risk for convulsive 
      activity with repeated administration.
FAU - Timofeeva, Olga A
AU  - Timofeeva OA
AD  - Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, 
      Durham, NC 27710, USA. timofeev@duke.edu
FAU - Levin, Edward D
AU  - Levin ED
LA  - eng
GR  - MH64494/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20080327
PL  - United States
TA  - Pharmacol Biochem Behav
JT  - Pharmacology, biochemistry, and behavior
JID - 0367050
RN  - 0 (Adrenergic alpha-Antagonists)
RN  - 0 (Excitatory Amino Acid Antagonists)
RN  - 0 (Nicotinic Agonists)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 6LR8C1B66Q (Dizocilpine Maleate)
RN  - 6M3C89ZY6R (Nicotine)
RN  - X4W3ENH1CV (Norepinephrine)
RN  - Y310PA316B (Idazoxan)
SB  - IM
MH  - Adrenergic alpha-Antagonists/*pharmacology
MH  - Animals
MH  - *Dizocilpine Maleate
MH  - *Excitatory Amino Acid Antagonists
MH  - Female
MH  - Idazoxan/*pharmacology
MH  - Maze Learning/drug effects
MH  - Memory/drug effects
MH  - Memory Disorders/*chemically induced/*psychology
MH  - Memory, Short-Term/drug effects
MH  - Nicotine/*antagonists & inhibitors/pharmacology
MH  - Nicotinic Agonists/*pharmacology
MH  - Norepinephrine/physiology
MH  - Psychomotor Performance/drug effects
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, N-Methyl-D-Aspartate/*antagonists & inhibitors
MH  - Seizures/chemically induced/psychology
MH  - Synaptic Transmission/drug effects
EDAT- 2008/05/06 09:00
MHDA- 2008/08/30 09:00
CRDT- 2008/05/06 09:00
PHST- 2007/08/15 00:00 [received]
PHST- 2008/02/20 00:00 [revised]
PHST- 2008/03/10 00:00 [accepted]
PHST- 2008/05/06 09:00 [pubmed]
PHST- 2008/08/30 09:00 [medline]
PHST- 2008/05/06 09:00 [entrez]
AID - S0091-3057(08)00099-3 [pii]
AID - 10.1016/j.pbb.2008.03.011 [doi]
PST - ppublish
SO  - Pharmacol Biochem Behav. 2008 Sep;90(3):372-81. doi: 10.1016/j.pbb.2008.03.011. 
      Epub 2008 Mar 27.