PAGE 1

University of Florida | Journal of Undergraduate Research | Volume 12 Issue 3 | Summer 2011 1 The Effects of Chronic Social Stress on a Rat M odel of Self Injurious Behavior Shannon L. Wolfman Amber M. Muehlmann, and Dr. Darragh P. Devine College of Liberal Arts and Sciences, University of Florida Self injurious behavior (SIB) is a debilitating c haracteristic of many developmental and genetic disorders. Common forms of SIB include self biting, head banging, self punching, and skin picking. Rats repeatedly treated with the psychostimulant drug pemoline exhibit self biting behavior, which closely re sembles the SIB seen in human self injurers. In these clinical populations, evidence suggests that emotional stress exacerbates SIB. Therefore, the effects of chronic social stress were examined in this rat mod el of SIB. The type of stress used, social def eat stress (SD), is a potent processive stressor which models the type of emotional stress that a human might experience. In this study, the chronically stressed rats exhibited larger areas of tissue damage due to SIB than did non stressed rats. There were no significant differences between the groups for self injurious oral contact or for incidence of SIB. Thus, stress increases the severity of self biting behavior but appears to have no effect on the time spent injuring or on whether or not SIB is initiat ed. INTRODUCTION Self injurious behavior (SIB) is a debilitating characteristic of many developmental and genetic disorders, such as autism and Lesch Nyhan syndrome. Common forms of SIB include self biting, head banging, self punching, and skin picking ( Thompson and Caruso, 2002 ). The effects of SIB are devastating For many patients, e ducation becomes nearly impossible, as does social interaction. Patients could also potentially cause themselves severe injury, and the emotional and financial burden on caretaker s is significant ( Matson et al., 2006; Matson and Nebel Schwalm, 2006 ). The neurochemical basis of SIB is unknown Although some treatments exist, many of those who self injure do not respond to any of them ( Anderson and Er nst, 1994; Un derwood et al., 198 9 ). R ats repeatedly treated with the psychostimulant drug pemoline begin to self injure (Kies and Devine, 2004). This self biting behavior is caused by biochemical changes in the brain such as alterations in neurotransmitter levels and receptors induced by pemoline, which is an indirect dopamine (DA) agonist. The injury that these rats express closely resembles SIB in human populations in that it seems compulsive and is c onfined to specific areas (Kies and Devine, 2004). Validity for th is animal model of SIB is also evidenced by individual diffe rences in the vulnerability to self injure that exists in both the rat and human populations (e.g. 30% of autistic children self injure) (Kies and Devine, 2004). Additionally, the drugs that have shown therapeutic benefits in human populations also protect rats from self injuring (Muehlmann et al. 2008 ). In human populations, stress has been reported to exacerbate SIB (Anderson and Ernst, 1994). Also, stress cross sensitizes with psychostimulants like amphetamine (Dietz et al., 2008), so stress likely also cross sensitizes with pemoline Since it seems that SIB may be a sensitization effect of pemoline (Muehlmann and Devine, 2008), we would expect an increase in SIB after repeated stress Therefor e, we explored the ef fects of chronic social defeat stress on SIB in the rat model. All aspects of the experiment were pre approved by the Institutiona l Animal Care and Use Committee. To produce chronic social stress, each rat was placed in an emotionally stressful environment in which a dominant male rat pins him. This type of stress, called social defeat (SD) stress is a potent processive stressor that more closely parallels the type of emotional stress that a human would experience than would a tail sh ock or some other systemic stressor (Huhman, 2006). Additionally, SD stress causes a dysregulation of the hypothalamic pituitary adrenal (HPA) axis ( Covington and Miczek, 2001) Self injurious human populations show a d ysregulation of stress hormones (Hessl et al., 2002; Curin et al., 2003). Another advantage of using SD stress is that rats do not habituate to it s stressful effects, so it maintains its potency over the entire period allowing for chronic stress (Dietz et al. 2008). Understanding the role that stress plays in SIB may help to develop more effective behavioral therapies and may also reveal underlyin g neurochemical mechanisms that can lead to improved phamacotherapies. METHODS Animals Experimental Animals (Intruders) Twenty three male Long Evans rats weighing between 150 g and 175 g when they arrived were pair housed during acclimation to the

PAGE 2

SHANNON WOLFMAN AMBER M M UEHLMANN AND D R DARRAGH P D EVINE University of Florida | Journal of Undergraduate Research | Volume 12 Issue 3 | Summer 2011 2 facility and the stress regimen They were given free access to standard rat chow and tap water and lived in a climate controlled environment. Their light dark cycle provided 12 hours of light and 12 hours of dark, and the lights were turned on at 6:00 AM. The rats were housed in standard polycarbonate cages (43 cm x 21.5 cm x 25.5 cm). Resident Animals Six male Long Evans rats, after vasectomies, were each housed with a cycling female Long Evans rat in a room separate from the experiment al animals. The male rats weighed 200 225g upon arrival. They were given the same free access to food and water that the intruder rats were given and housed in the same types of cages. Their light/dark cycle was reversed, however, with 12 hours of dark st arting at 6:00 AM. All procedures were conducted in accordance with the Guide for the Care and Use of Laboratory Animals. Social Defeat The residents were housed with their females for at least two weeks before social defeat began. The residents were trained to exhibit dominant behavior. At 7:00 AM, during her cage and the male left alone for ten minutes. Then, an The intruder was considered defe ated if he displayed a supine posture with the resident rat on top of him for at least three seconds. After either three defeats or five minutes, whichever came first, the intruder was removed from the layere d wire mesh cage (10 cm x 10 cm x 15 cm). The wire cage with the intruder inside was then placed inside the The wire cage allowed for continued indirect contact with the resident. Each intruder wa s exposed to social defeat for 12 days in a row. The schedules were made so that each intruder saw each resident only twice and only after six days. The rats that were part of the non stressed group were handled for two minutes each for every day of so cial defeat. Drug Treatment Pemoline (2 amino 5 phenyl 1,3 oxazol 4 one; Spec trum Chemicals, New Brunswick, New Jersey) was suspended at a concentration of 50 mg/ml in peanut oil. The pemoline and peanut oil were left stirring overnight to make sure the pemoline was in suspension. The day following the last day of social defeat, the rats were each weighed and injected with 150 mg/kg of pemoline each morning for five days. The injections were administered subcutaneously on either flank, changing sides ea ch day. Assessing Self Injury and Stereotopy Each rat was shown to a camera every morning before injections and every afternoon to record any injury (denuded skin, erythema, edema, or open lesion). Any rat with an open lesion was immediately euthanized. Images from the video allowed the computer program MCID software (Imaging Research Inc., St. Catherines, ON, Canada) to evaluate the size of the injury in mm 2 The rats were video taped in five minute segments every three hours throughout the duratio n of pemoline treatment to get a random, representative sample of their behaviors throughout the day and night. A trained observer then quantif i ed the behaviors. Any oral contact that stayed on the same part of the body for more than two seconds counted as self injurious oral contact. Grooming was considered to be sustained oral contact that did not focus on the same part of the body for more than two seconds. Stereotyped behavior was considered to be head bobbing or licking of the cage floor. The durat ion of each behavior was summed over the day and divided by 2400 seconds, the total number of seconds recorded in a day. Statistics Repeated measures analyses of variance (RM ANOVA) was used to determine between group differences in self injurious oral contact, size of tissue damage, and stereotopy, which were treated as statistically reliable when the p values were less than 0.05. All significant effects were further analyzed with pre significant difference (LSD) post tests. Missing data from the four rats that were euthanized before the conclusion of the experiment were replaced by repeating the final datum obtained from each rat for each measure. RESULTS Rats that are repeatedly injected with pemoline exhibit self biting behavior (Fig ure 1A). All rats, regardless of past SD stress exposure, exhibited SIB in response to this dose of pemoline (150 mg/kg) (Fig ure 1A), indicating that stress history does not affect incidence or onset of self injury. However, rats that were exp osed SD stress exhibited significantly larger areas of tissue damage due to SIB than did rats that were not exposed to SD stress [F (10,210) = 2.095, p < 0.05] (Fig ure 1B). This suggests that stress exposure increases the severity of SIB. Stress history als o did not affect self injurious oral contact (i.e. time spent injuring) (Fig ure 1C) or other pemoline induced stereotopies (Fig ure 1D). Inter observer reliability was r = 0.9647 for the duration of oral contact and r = 0.9306 for the duration of stereotypy and was determined a Pearson correlation. These results suggest that stress does not affect the onset or duration of pemoline induced behaviors, including SIB.

PAGE 3

THE EFFECTS OF CHRON IC SOCIAL S TRESS ON A RAT M ODEL OF SELF INJURIOUS B EHAVIOR University of Florida | Journal of Undergraduate Research | Volume 12 Issue 3 | Summer 2011 3 Figure 1 : Effects of social defeat stress on pemoline induced self injurious behavior. All pemoline treated rats exhibited self injurious behavior regardless of stress history (A). Stressed rats showed significantly larger areas of tissue damage due to self injury than did non stressed rats (B). Stress history did not affect the duration of self injurious oral contact (C). Stress history did not affect other pemoline induced stereotopies (D). All values are expressed as group means S.E.M. (* p < 0.05). DISCUSSION Since all rats regard less of stress history exhibited SIB, it can be concluded that the dose of pemoline used and not the effects of stress account for the incidence of SIB. Since the stressed group of rats displayed significantly larger areas of tissue damage due to pemoline induced SIB compared with the non stressed group, but did not spend any more time engaged in pemoline induced self injurious oral contact than did the non stressed group of rats, we can conclude that stress enhanced the severity but not the duration of SIB Our findings that stress exacerbates SIB are congruent with similar findings in clinical populations of self injurers (Anderson and Ernst, 1994). This suggests that relieving and minimizing the stress on patients may help to ameliorate their self injury. Evidence indicates that glu tamate plays a role in pemoline induced SIB (Muehlmann et al., 2008). The glutamatergic system is responsible for the sensitizing effects of cocaine and amphetamine (Wolf, 1998), suggesting that SIB might be a sensitized respons e to the effects of pemoline. The effect of stress on the severity of the self biting behavior supports this idea, since SD stress cross sensitizes with psychostimulants (Dietz et al. 2008). Since this study indicates that sensitization and stress play an important role in SIB, f uture studies will focus on the role of glutamate in pemoline induced behavioral sensitization and how it relates to the interactions between SIB and dysregulation of the HPA axis Learning more about the neurobiological mechanism s that mediate pemoline induced SIB can help us to develop more effective treatment strategies for human populations of self injurers.

PAGE 4

SHANNON WOLFMAN AMBER M M UEHLMANN AND D R DARRAGH P D EVINE University of Florida | Journal of Undergraduate Research | Volume 12 Issue 3 | Summer 2011 4 REFERENCES Anderson L, Ernst, M ( 1994 ) Self injury in Lesch Nyhan Disease. J Autism Dev Disor d 24 : 67 81. Covingt on HE, Miczek KA ( 2001 ) Repeated social defeat stress, cocaine or morphine: Effects on behavioral sensitization and intravenous cocaine self administration "binges ." Psychopharm aco l 158 : 388 398. Curin J, Terzic J, Petkovic Z, Zekan L, Terzic I, Susnjara I ( 2003 ) Lower cortisol and higher ACTH levels in individuals with autism. J Autism Dev Disor d 33 : 443 448. Dietz D, Dietz K Moore S, Ouimet C, Kabbaj M ( 2008 ) Repeated social defeat stress induced sensitization to the locomotor activating effects of d amphe tamine: role of individual diff erences. Psychopharmacol 198 : 51 62. Hessl D, Glaser B, Dyer Friedman J, Blasey C, Hastie T, Gunnar M, Reiss A ( 2002 ) Cortisol and behavior in fragile X syndro me. Psychoneuroendocrinology 27 : 855 872. Huhman KL ( 2006 ) Social co nflict models: Can th ey inform us about human psychop ath ology? Horm Beha v 50 : 640 646. Kies SD, Devine DP ( 2004 ) Self injurious behaviour: a comparison of caffeine and pemoline models in rats. Pharmacol Biochem Beha v 79 : 587 598. Matson J L, Minshawi NF, Gonz alez ML, Mayville SB (2006) The relationship of comorbid problem behaviors to social skills in persons with profound mental retardation. Behav Modif 30 :496 506. Matson JL, Nebel Schwalm M (2007) Assessing challenging behaviors in children with autism spect rum disorders: A review. Res Dev Disabil 28 :567 579. Muehlmann AM, Brown BD, Devine D P ( 2008 ) Pemoline (2 amino 5 phenyl 1,3 oxazol 4 one) induced self injurious behavior: a rodent model of pharmacotherapeutic efficacy. J Pharmacol Exp Ther 324 (1):214 23. Muehlmann AM, Devine DP ( 2008 ) Glutamate mediated neuroplasticity in an animal model of self injurious behaviour. Behav Brain Res 189 : 32 40. Thompson T Caruso M (2002) Self injury: knowing what we're looking for, in Self Injurious Behavior: Gene Brain B ehavior Relationships 3 21 Underwood LA, Figueroa RG, Thyer BA, Nzeocha A (1989) Interruption and DRI in the treatment of self injurious behavior among mentally retarded and autistic self restrainers. Be hav Modif 13 :471 481 Wolf ME ( 1998 ) The role of e xcitatory amino acids in behavioral sensitization to psychomotor stimulant s. Prog Neurobiol 54 : 679 720.


Summer Focus on Medical Research : The Effects of Chronic Social Stress on a Rat Model of Self-Injurious Behavior
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Title: Summer Focus on Medical Research : The Effects of Chronic Social Stress on a Rat Model of Self-Injurious Behavior
Series Title: Journal of Undergraduate Research
Physical Description: Serial
Language: English
Creator: Wolfman, Shannon L.
Muehlmann, Amber M.
Devine, Darragh P.
Publisher: University of Florida
Place of Publication: Gainesville, Fla.
Publication Date: 2011
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Abstract: Self injurious behavior (SIB) is a debilitating characteristic of many developmental and genetic disorders. Common forms of SIB include self-biting, head-banging, self-punching, and skin-picking. Rats repeatedly treated with the psychostimulant drug pemoline exhibit self-biting behavior, which closely resembles the SIB seen in human self-injurers. In these clinical populations, evidence suggests that emotional stress exacerbates SIB. Therefore, the effects of chronic social stress were examined in this rat model of SIB. The type of stress used, social defeat stress (SD), is a potent processive stressor which models the type of emotional stress that a human might experience. In this study, the chronically stressed rats exhibited larger areas of tissue damage due to SIB than did non-stressed rats. There were no significant differences between the groups for self-injurious oral contact or for incidence of SIB. Thus, stress increases the severity of self-biting behavior but appears to have no effect on the time spent injuring or on whether or not SIB is initiated.
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The Effects of Chronic Social Stress on a Rat Model of Self-

Injurious Behavior

Shannon L. Wolfman, Amber M. Muehlmann, and Dr. Darragh P. Devine

College of Liberal Arts and Sciences, University of Florida

Self injurious behavior (SIB) is a debilitating characteristic of many developmental and genetic disorders. Common forms of SIB
include self-biting, head-banging, self-punching, and skin-picking. Rats repeatedly treated with the psychostimulant drug pemoline
exhibit self-biting behavior, which closely resembles the SIB seen in human self-injurers. In these clinical populations, evidence
suggests that emotional stress exacerbates SIB. Therefore, the effects of chronic social stress were examined in this rat model of SIB.
The type of stress used, social defeat stress (SD), is a potent processive stressor which models the type of emotional stress that a
human might experience. In this study, the chronically stressed rats exhibited larger areas of tissue damage due to SIB than did non-
stressed rats. There were no significant differences between the groups for self-injurious oral contact or for incidence of SIB. Thus,
stress increases the severity of self-biting behavior but appears to have no effect on the time spent injuring or on whether or not SIB is
initiated.


INTRODUCTION

Self-injurious behavior (SIB) is a debilitating
characteristic of many developmental and genetic
disorders, such as autism and Lesch-Nyhan syndrome.
Common forms of SIB include self-biting, head-banging,
self-punching, and skin-picking (Thompson and Caruso,
2002). The effects of SIB are devastating. For many
patients, education becomes nearly impossible, as does
social interaction. Patients could also potentially cause
themselves severe injury, and the emotional and financial
burden on caretakers is significant (Matson et al., 2006;
Matson and Nebel-Schwalm, 2006). The neurochemical
basis of SIB is unknown. Although some treatments exist,
many of those who self-injure do not respond to any of
them (Anderson and Ernst, 1994; Underwood et al., 1989).
Rats repeatedly treated with the psychostimulant drug
pemoline begin to self-injure (Kies and Devine, 2004).
This self-biting behavior is caused by biochemical changes
in the brain, such as alterations in neurotransmitter levels
and receptors induced by pemoline, which is an indirect
dopamine (DA) agonist. The injury that these rats express
closely resembles SIB in human populations in that it
seems compulsive and is confined to specific areas (Kies
and Devine, 2004). Validity for this animal model of SIB is
also evidenced by individual differences in the
vulnerability to self-injure that exists in both the rat and
human populations (e.g., 30% of autistic children self
injure) (Kies and Devine, 2004). Additionally, the drugs
that have shown therapeutic benefits in human populations
also protect rats from self injuring (Muehlmann et al.,
2008). In human populations, stress has been reported to
exacerbate SIB (Anderson and Ernst, 1994). Also, stress
cross-sensitizes with psychostimulants like amphetamine


(Dietz et al., 2008), so stress likely also cross-sensitizes
with pemoline. Since it seems that SIB may be a
sensitization effect of pemoline (Muehlmann and Devine,
2008), we would expect an increase in SIB after repeated
stress. Therefore, we explored the effects of chronic social
defeat stress on SIB in the rat model. All aspects of the
experiment were pre-approved by the Institutional Animal
Care and Use Committee.
To produce chronic social stress, each rat was placed in
an emotionally stressful environment in which a dominant
male rat pins him. This type of stress, called social defeat
(SD) stress, is a potent processive stressor that more
closely parallels the type of emotional stress that a human
would experience than would a tail shock or some other
systemic stressor (Huhman, 2006). Additionally, SD stress
causes a dysregulation of the hypothalamic-pituitary-
adrenal (HPA) axis (Covington and Miczek, 2001). Self-
injurious human populations show a dysregulation of stress
hormones (Hessl et al., 2002; Curin et al., 2003). Another
advantage of using SD stress is that rats do not habituate to
its stressful effects, so it maintains its potency over the
entire period, allowing for chronic stress (Dietz et al.,
2008). Understanding the role that stress plays in SIB may
help to develop more effective behavioral therapies and
may also reveal underlying neurochemical mechanisms
that can lead to improved phamacotherapies.

METHODS

Animals

Experimental Animals (Intruders). Twenty-three male
Long Evans rats weighing between 150g and 175g when
they arrived were pair housed during acclimation to the


University of Florida I Journal of Undergraduate Research I Volume 12, Issue 3 1 Summer 2011
1





SHANNON WOLFMAN, AMBER M. MUEHLMANN, AND DR. DARRAGH P. DEVINE


facility and the stress regimen. They were given free access
to standard rat chow and tap water and lived in a climate-
controlled environment. Their light dark cycle provided 12
hours of light and 12 hours of dark, and the lights were
turned on at 6:00 AM. The rats were housed in standard
polycarbonate cages (43 cm x 21.5 cm x 25.5 cm).

Resident Animals. Six male Long Evans rats, after
vasectomies, were each housed with a cycling female Long
Evans rat in a room separate from the experimental
animals. The male rats weighed 200-225g upon arrival.
They were given the same free access to food and water
that the intruder rats were given and housed in the same
types of cages. Their light/dark cycle was reversed,
however, with 12 hours of dark starting at 6:00 AM. All
procedures were conducted in accordance with the Guide
for the Care and Use of Laboratory Animals.

Social Defeat

The residents were housed with their females for at least
two weeks before social defeat began. The residents were
trained to exhibit dominant behavior. At 7:00 AM, during
the residents' dark schedule, a female was removed from
her cage and the male left alone for ten minutes. Then, an
intruder rat was placed inside the resident's cage. The
intruder was considered defeated if he displayed a supine
posture with the resident rat on top of him for at least three
seconds. After either three defeats or five minutes,
whichever came first, the intruder was removed from the
resident's cage and placed into a small, double-layered
wire mesh cage (10 cm x 10 cm x 15 cm). The wire cage
with the intruder inside was then placed inside the
resident's cage for the remainder of the ten minute period.
The wire cage allowed for continued indirect contact with
the resident. Each intruder was exposed to social defeat for
12 days in a row. The schedules were made so that each
intruder saw each resident only twice and only after six
days. The rats that were part of the non-stressed group
were handled for two minutes each for every day of social
defeat.

Drug Treatment

Pemoline (2-amino-5-phenyl-l,3-oxazol-4-one; Spec-
trum Chemicals, New Brunswick, New Jersey) was
suspended at a concentration of 50 mg/ml in peanut oil.
The pemoline and peanut oil were left stirring overnight to
make sure the pemoline was in suspension.
The day following the last day of social defeat, the rats
were each weighed and injected with 150 mg/kg of
pemoline each morning for five days. The injections were
administered subcutaneously on either flank, changing
sides each day.


Assessing Self Injury and Stereotopy

Each rat was shown to a camera every morning before
injections and every afternoon to record any injury
(denuded skin, erythema, edema, or open lesion). Any rat
with an open lesion was immediately euthanized. Images
from the video allowed the computer program MCID
software (Imaging Research Inc., St. Catherines, ON,
Canada) to evaluate the size of the injury in mm2
The rats were videotaped in five-minute segments every
three hours throughout the duration of pemoline treatment
to get a random, representative sample of their behaviors
throughout the day and night. A trained observer then
quantified the behaviors. Any oral contact that stayed on
the same part of the body for more than two seconds
counted as self-injurious oral contact. Grooming was
considered to be sustained oral contact that did not focus
on the same part of the body for more than two seconds.
Stereotyped behavior was considered to be head bobbing or
licking of the cage floor. The duration of each behavior
was summed over the day and divided by 2400 seconds,
the total number of seconds recorded in a day.

Statistics

Repeated measures analyses of variance (RM-ANOVA)
was used to determine between group differences in self-
injurious oral contact, size of tissue damage, and
stereotopy, which were treated as statistically reliable when
the p-values were less than 0.05. All significant effects
were further analyzed with pre-planned Fisher's least
significant difference (LSD) post-tests. Missing data from
the four rats that were euthanized before the conclusion of
the experiment were replaced by repeating the final datum
obtained from each rat for each measure.

RESULTS

Rats that are repeatedly injected with pemoline exhibit
self-biting behavior (Figure 1A). All rats, regardless of past
SD stress exposure, exhibited SIB in response to this dose
of pemoline (150 mg/kg) (Figure 1A), indicating that stress
history does not affect incidence or onset of self-injury.
However, rats that were exposed SD stress exhibited
significantly larger areas of tissue damage due to SIB than
did rats that were not exposed to SD stress [F(10,210) =
2.095, p < 0.05] (Figure 1B). This suggests that stress
exposure increases the severity of SIB. Stress history also
did not affect self-injurious oral contact (i.e. time spent
injuring) (Figure 1C) or other pemoline-induced
stereotopies (Figure ID). Inter-observer reliability was r =
0.9647 for the duration of oral contact and r = 0.9306 for
the duration of stereotypy and was determined a Pearson
correlation. These results suggest that stress does not affect
the onset or duration of pemoline-induced behaviors,
including SIB.


University of Florida I Journal of Undergraduate Research I Volume 12, Issue 3 I Summer 2011
2





THE EFFECTS OF CHRONIC SOCIAL STRESS ON A RAT MODEL OF SELF-INJURIOUS BEHAVIOR


--- stress
-D- no stress


0
1- 4-













S0



0
-4


0 1 2 3 4 5
day


4E
E
E
0




4-
0
4)
CU

N









0


o
0-
01

4-
0i


1 2 3 4 5 6
day


0 1 2 3 4 5


Figure 1: Effects of social defeat stress on pemoline-induced self-injurious behavior. All pemoline-treated rats
exhibited self-injurious behavior regardless of stress history (A). Stressed rats showed significantly larger areas of
tissue damage due to self-injury than did non-stressed rats (B). Stress history did not affect the duration of self-
injurious oral contact (C). Stress history did not affect other pemoline-induced stereotopies (D). All values are
expressed as group means S.E.M. (* p < 0.05).


DISCUSSION

Since all rats regardless of stress history exhibited SIB, it
can be concluded that the dose of pemoline used and not
the effects of stress account for the incidence of SIB. Since
the stressed group of rats displayed significantly larger
areas of tissue damage due to pemoline-induced SIB
compared with the non-stressed group, but did not spend
any more time engaged in pemoline-induced self-injurious
oral contact than did the non-stressed group of rats, we can
conclude that stress enhanced the severity but not the
duration of SIB. Our findings that stress exacerbates SIB
are congruent with similar findings in clinical populations
of self injurers (Anderson and Ernst, 1994). This suggests
that relieving and minimizing the stress on patients may
help to ameliorate their self-injury.


Evidence indicates that glutamate plays a role in
pemoline-induced SIB (Muehlmann et al., 2008). The
glutamatergic system is responsible for the sensitizing
effects of cocaine and amphetamine (Wolf, 1998),
suggesting that SIB might be a sensitized response to the
effects of pemoline. The effect of stress on the severity of
the self-biting behavior supports this idea, since SD stress
cross sensitizes with psychostimulants (Dietz et al., 2008).
Since this study indicates that sensitization and stress play
an important role in SIB, future studies will focus on the
role of glutamate in pemoline-induced behavioral
sensitization and how it relates to the interactions between
SIB and dysregulation of the HPA axis. Learning more
about the neurobiological mechanisms that mediate
pemoline-induced SIB can help us to develop more
effective treatment strategies for human populations of
self-injurers.


University of Florida I Journal of Undergraduate Research I Volume 12, Issue 3 I Summer 2011
3


1 2 3 4 5 6
day





SHANNON WOLFMAN, AMBER M. MUEHLMANN, AND DR. DARRAGH P. DEVINE


REFERENCES

Anderson L, Ernst, M (1994) Self-injury in Lesch-Nyhan Disease. JAutism Dev
Disord24:67-81.

Covington HE, Miczek KA (2001) Repeated social-defeat stress, cocaine or
morphine: Effects on behavioral sensitization and intravenous cocaine self-
administration "binges." . ;, ." ;. .' 158:388-398.

Curin J, Terzic J, Petkovic Z, Zekan L, Terzic I, Susnjara I (2003) Lower cortisol
and higher ACTH levels in individuals with autism. J Autism Dev Disord
33:443-448.

Dietz D, Dietz K, Moore S, Ouimet C, Kabbaj M (2008) Repeated social defeat
stress-induced sensitization to the locomotor activating effects of d-
amphetamine: role of individual differences. :. :., ,;;. .' 198:51-62.

Hessl D, Glaser B, Dyer-Friedman J, Blasey C, Hastie T, Gunnar M, Reiss A
(2002) Cortisol and behavior in fragile X syndrome.
S. 27:855-872.

Huhman KL (2006) Social conflict models: Can they inform us about human
psychopathology? Horm Behav 50:640-646.


Matson JL, Minshawi NF, Gonzalez ML, Mayville SB (2006) The relationship of
comorbid problem behaviors to social skills in persons with profound mental
retardation. Behav 311 4- ...506.

Matson JL, Nebel-Schwalm M (2007) Assessing challenging behaviors in
children with autism spectrum disorders: A review. Res Dev Disabil 28:567-
579.

Muehlmann AM, Brown BD, Devine DP (2008) Pemoline (2-amino-5-phenyl-
1,3-oxazol-4-one)-induced self-injurious behavior: a rodent model of
pharmacotherapeutic efficacy. J Pharmacol Exp Ther 324(1):214-23.

Muehlmann AM, Devine DP (2008). Glutamate-mediated neuroplasticity in an
animal model of self-injurious behaviour. Behav Brain Res 189:32-40.

Thompson T, Caruso M (2002) Self-injury: knowing what we're looking for, in
Behavior: Gene-Brain-Behavior Relationships, 3-21.

Underwood LA, Figueroa RG, Thyer BA, Nzeocha A (1989) Interruption and
DRI in the treatment of self-injurious behavior among mentally retarded and
autistic self-restrainers. Behav 1 13 471-481.

Wolf ME (1998) The role of excitatory amino acids in behavioral sensitization to
psychomotor stimulants. Prog Neurobiol 54:679-720.


Kies SD, Devine DP (2004) Self-injurious behaviour: a comparison of caffeine
and pemoline models in rats. PharmacolBiochem Behav 79:587-598.






















































University of Florida I Journal of Undergraduate Research I Volume 12, Issue 3 1 Summer 2011
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Last updated May 24, 2011 - Version 3.0.2 - mvs