Alcohol, Vol. 18, Nos. 2/3, pp. 123–130, 1999
© 1999 Elsevier Science Inc.
Printed in the USA. All rights reserved
0741-8329/99/$–see front matter
Nicotine Blocks Ethanol and Diazepam
Impairment of Air Righting and Ethanol
Impairment of Maze Performance
HARRY A. TRACY, JR., MATTHEW J. WAYNER AND DEBORAH L. ARMSTRONG
Division of Life Sciences, The University of Texas at San Antonio, San Antonio, TX
Received 16 October 1998; Accepted 17 November 1998
TRACY, H. A. JR., M. J. WAYNER AND D. L. ARMSTRONG.
Nicotine blocks ethanol and diazepam impairment
of air righting and ethanol impairment of maze performance.
(2/3) 123–130, 1999.—Results of our previous re-
search in rats demonstrate the following: (a) Angiotensin II (Ang II) inhibits long term potentiation (LTP) in dentate granule
cell–perforant path synapses and that this inhibition can be blocked by losartan, an Ang II AT
receptor antagonist; (b) both
ethanol and diazepam inhibit LTP induction and this inhibition can be blocked by losartan; (c) impairment of air righting by
ethanol and diazepam (DZ) and eight-arm radial maze performance by ethanol can be blocked by pretreatment with losar-
tan; (d) inhibition of dentate granule cell LTP by Ang II can also be prevented by pretreatment with nicotine. Therefore, it
seemed reasonable to hypothesize that ethanol and diazepam impairment of air righting and maze performance might also be
blocked by pretreatment with nicotine. The purpose of the present study was to determine the effects of nicotine 0.1, 0.2, 0.3,
and 0.4 mg/kg subcutaneously (SC) on 2.0 g/kg ethanol per os (PO) and 1.0 and 2.0 mg/kg DZ intraperitoneally (IP) induced
impairment of air righting; and to determine if the impaired maze performance due to 2.0 g/kg ethanol PO could be pre-
vented by pretreatment with 0.4 mg/kg of nicotine, SC. Results confirm the hypothesis that moderate doses of ethanol, 2.0 g/
kg PO, and DZ, 1.0 mg/kg IP, impair air righting and that the impairment can be prevented by pretreatment with nicotine SC.
Nicotine was not effective in blocking the 2.0 mg/kg DZ impairment of air righting. Nicotine, 0.4 mg/kg SC, prevented the im-
paired maze performance induced by 2.0 g/kg ethanol PO. © 1999 Elsevier Science Inc. All rights reserved.
Nicotine Ethanol Diazepam Air righting Maze learning
IN 1991 we reported that angiotensin II (Ang II) inhibits the
induction of hippocampal long term potentiation (LTP) in
medial perforant path–dentate granule cell synapses (13) and
that the inhibition can be prevented by pretreatment with
losartan, an Ang II AT
receptor antagonist (56). Hippocam-
pal LTP is a type of frequency-dependent synaptic plasticity
related to learning, memory, and other cognitive processes.
Both ethanol and the benzodiazepines reduce anxiety, induce
sedation, and produce complex amnesic effects in humans
(7,11,26,27,29,52). Ethanol and diazepam (DZ) are well
known for inducing anterograde amnesia for short term mem-
ory. Both of these drugs definitely inhibit hippocampal LTP
(55). We were able to show that these inhibitory effects were
mediated by Ang II because the inhibition was blocked by
pretreatment with losartan. Also, we have demonstrated that
the impairment of air righting by ethanol (50) and DZ (49)
can be prevented by pretreatment with losartan. Air righting
under normal conditions in the rat is a complex perceptual-
motor response involving visual cues and prior experience
(36). Normal air righting might therefore require a normal
functioning hippocampus. More complex behaviors such as
maze performance in the rat are impaired by ethanol, and are
known to depend upon normal hippocampal function; the im-
pairment produced by ethanol can be prevented by pretreat-
ment with losartan (51).
Nicotine and particularly tobacco smoking can modulate
many complex and important physiological functions: alert-
ness, arousal, and attention (15,21,34,42); learning and mem-
ory (20,22,24,25); anxiety (9,18,45); depression (8); stress (35);
schizophrenia (3,4,16,17,47); Alzheimer’s and Parkinson’s dis-
eases (6,21,23,28,32,33,37,38,40,46,53); and analgesia (12,39).
Recently, chewing nicotine gum and nicotine transdermal
Requests for reprints should be addressed to Matthew J. Wayner, Ph.D., Division of Life Sciences, The University of Texas at San Antonio,
6900 North Loop 1604 West, San Antonio, TX 78249-0662. Tel: (210) 458-4481; Fax: 210-458-4510; E-mail: firstname.lastname@example.org