Figure 2. Rotarod performance following saline or yohimbine

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Transcript Figure 2. Rotarod performance following saline or yohimbine

The Effects of Yohimbine on Ethanol Consumption and Motor
Coordination in CD-1 Male Mice
Rafael Perez*, Ronald Kaltreider, and Bradley Rehnberg, Department of Biology,
York College of Pennsylvania, York Pa 17405
Yohimbine
Introduction
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The link between stress and alcohol abuse is well
documented. Individuals who experience a higher
incidence of stressful life events are more likely to
abuse alcohol and relapse (Brown et al. 1995).
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A)
B)
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ns
To investigate the link between stress and alcohol
abuse, physiological and behavioral techniques have
been used as stressors. However, the results derived
from such techniques are conflicting (Croft et al. 2005;
Findler and Lolordo, 1996).
Accelerating Rotarod
Yohimibine is an alpha-2 adrenoceptor antagonist that
produces stress by increasing levels of norepinephrine
and antagonizing GABA (Dunn and Corbett 1992).
Yohimbine potentiates the motor-impairing effects of
depressants (Sӧderpalm and Engel 1989). However, the
observed deficits in motor coordination may be due to
differences in drug administration and dosage (Drugan
et al. 1996).
To date, most studies have focused on the effects of
yohimbine on ethanol reinstatement following extensive
periods of operant conditioning (Simms et al. 2011).
The effects of yohimbine on voluntary ethanol
consumption and motor coordination are yet to be
determined.
Objectives
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Yohimbine decreases ethanol but not water
consumption
Determine the effects of yohimbine on voluntary
ethanol consumption in male CD-1 mice
Determine the effects of the interaction between
yohimbine and ethanol on motor coordination by
performing an accelerating rotarod test
Results and Discussion
Figure 1. Water and ethanol consumption following saline or
yohimbine injections. Values reported are the percent difference of
consumption between bottles: A) water and water. B) water and EtOH (10 %
v/v) .There was significant difference in ethanol consumption between mice
injected with yohimbine and saline during sessions 4 and 5 (f= 10.15, p< 0.05,
via repeated measures two-way ANOVA). Neither Session nor the interaction
had a significant effect on ethanol consumption ( fS = 1. 783, p > 0.05; fT =
0.5641, p > 0.05). Error bars indicate 95 % CI. Asterisk represent significance.
Yohimbine does not affect motor coordination
A)
B)
ns
ns
ns
ns
Methods
CD-1 male mice (n = 18)
Withhold food and water 3
hours prior to testing
Saline
injection ( i. p.)
(n = 9)
2-bottle choice
test:
water/water
(n= 5)
Yohimbine injection
(2 mg/kg i. p.) (n = 9)
2- bottle
choice test:
EtOH 10 % /
water
(n = 4)
2-bottle choice
test:
water/water
(n= 5)
Record fluid consumption
60 minutes after
injections (n = 18)
Rotarod test:
5 trial, 45 rpm, record latency to
fall (n = 18 )
2- bottle
choice test:
EtOH 10 % /
water
(n = 4)
Figure 2. Rotarod performance following saline or yohimbine
injections and access to diffent fluids. A) water and water. B) water and
EtOH (10 % v/v). Treatment or session had no significant effects on latency
to fall (fT=0.7017, p>0.05; fS= 0.8545, p>0.05 via repeated measures twoway ANOVA). The interaction between treatment and session was significant
(fI=4.206, p<0.05). Error bars indicate 95 % CI.
• Yohimbine decreased ethanol consumption in CD-1 male
mice during the last two weeks of the experiment (Figure 1).
• Yohimbine had no effect on rotarod performance (Figure 2).
• One possible explanation for the observed results is that
mice created an association between the adverse effects of
the yohimbine injections and the novel ethanol stimulus
(Cunningham et al. 2002).
Future Studies
To determine the effects of yohimbine on brain regions
involved in dependence-related behaviors by measuring
phosphorylation status of the neural marker of activity, c-fos,
following the two-bottle choice test.
References
Brown, S., Vik, P., Patterson, T., Grant, I., & Schuckit, M. (1995). Stress, vulnerability and adult alcohol
relapse. Journal Of Studies On Alcohol, 56(5), 538-545.
Croft, A., Brooks, S., Cole, J., & Little, H. (2005). Social defeat increases alcohol preference of C57BL/10
strain mice; effect prevented by a CCKB antagonist. Psychopharmacology, 183(2), 163-170.
Cunningham, C. L., Clemans, J. M., & Fidler, T. L. (2002). Injection timing determines whether
intragastric ethanol produces conditioned place preference or aversion in mice. Pharmacology
Biochemistry And Behavior, 72(3), 659-668.
Drugan, R., Coyle, T., Healy, D. and Chen, S. (1996). Stress controllability influences the ataxic properties
of both ethanol and midazolam in the rat. Behavioral Neuroscience, 110 (2), 360-367. doi: 07357044/96/S3.00
Dunn, R., & Corbett, R. (1992). Yohimbine-induced seizures involve NMDA and GABAergic transmission.
Neuropharmacology, 31(4), 389-395.
Fidler, T. L., & Lolordo, V. M. (1996). Failure to find postshock increases in ethanol preference.
Alcoholism Clinical And Experimental Research, 20(1), 110-121.
Simms, J., Richards, J., Mill, D., Kanholm, I., Holgate, J., & Bartlett, S. (2011). Induction of multiple
reinstatements of ethanol- and sucrose-seeking behavior in Long-Evans rats by the α-2
adrenoreceptor antagonist yohimbine. Psychopharmacology, 218(1), 101-110.
Sӧderpalm, B. and Engel, J. (1989). α2-Adrenoceptor antagonists potetiate the anticonflict and the
rotarod impairing effects of benzodiazepine. Journal of Neurotransmission, 76, 191-204.
Acknowledgements
I would like to thank Derek Andenson, Grant Glatfelter, Suzanne Chouljian and Kyle Ilgenfritz for their assistance with the
animals. I also would like to thank Dr. Jessica Boyette-Davis for her guidance and support, and Dr. Bridgette Hagerty for
helping with the statistical analysis. Finally, I would like to thank the extended faculty of the Biology Department at: