Stress hormone exposure induces anhedonic-like behavior in adult male rats but not in adolescent...

1
ACKNOWLEDGEMENTS Thanks to The Foundation of Hope and NIAAA grant AA019682 to JB and the Bowles Center for Alcohol Studies for making this work possible I NTRODUCTION ARC EXPRESSION CONCLUSIONS POST 7-D CORT POST 21-D CORT PROCEDURE POST 14-D CORT Stress has been shown to be a major predictor in the onset of various neuropsychological disorders including major depressive disorder (MDD). A core symptom of MDD is anhedonia or a loss of interest/pleasure in normally rewarding activities. However little is known about how stress exposure during the adolescent developmental period affects the emergence of anhedonia and how this differs from stress exposure in adulthood. Using an animal model we have previously shown anhedonic-like behavior in male adult rats following chronic exposure to the stress hormone corticosterone (CORT). Thus, the aim of this work is to explore the relationship between CORT exposure and anhedonic-like behavior as measured by sucrose intake tests in adolescent and adult male rats. Adolescent (PND 28) and adult (PND 70) rats were exposed to CORT (0.3 mg/ml) for 21 days. Sucrose intake tests were conducted weekly to measure anhedonic-like behavior. Here we show that chronic CORT exposure does indeed predict a significant decrease in sucrose intake in adult male rats; however, this effect was not observed in adolescent male rats. These results suggest that there are underlying molecular mechanisms that protect adolescent male rats from the development of anhedonic-like behavior following CORT exposure. Immunohistochemical analyses of Arc expression- an immediate early gene and marker for neural plasticity-were conducted to identify the underlying molecular mechanisms of this effect. Figure 3: SI test conducted following 7 days of CORT and water exposure revealed a significant decrease in sucrose intake among adult rats exposed to CORT but not water. This effect was not observed in adolescent rats. *p<0.05 Figure 5: SI test conducted following 21 days of CORT and water exposure revealed a significant decrease in sucrose intake among adult rats exposed to CORT but not water. This effect was not observed in adolescent rats. *p<0.05 Figure 4: SI test conducted following 14 days of CORT and water exposure revealed a significant decrease in sucrose intake among adult rats exposed to CORT but not water. This effect was not observed in adolescent rats. *p<0.05 Stress hormone exposure induces anhedonic-like behavior in adult male rats but not in adolescent rats. B. Fortino, V. Agan, A.A. Jaramillo, J. Besheer Bowles Center for Alcohol Studies, Department of Psychiatry, University of North Carolina at Chapel Hill Psychology Department Sponsor: Dr. Charlotte Boettiger PrL Sucrose (0.5% w/v) Intake (ml/kg) 0 5 10 15 20 25 Water CORT Adolescent Adult Sucrose (0.5% w/v) Intake (ml/kg) 0 5 10 15 20 25 Water CORT Adolescent Adult * Sucrose (0.5% w/v) Intake (ml/kg) 0 5 10 15 20 25 Water CORT Adolescent Adult * * BL SI SI SI 7-d CORT/H2O 14-d CORT/H2O 21-d CORT/H2O Figure 1: Adolescent (PND 28) and adult (PND 70) male Long Evans rats were given a baseline (BL) sucrose intake (SI) test. Adult and adolescent rats were then given a bottle containing a CORT solution (0.3 mg/ml) or H 2 O for 21 days. Weekly sucrose intake (SI) tests were conducted WEIGHTS A B C D Figure 2: Daily average weight of adolescent and adult rats during water and CORT exposure did not differ among age group. Figure 6: (A) Atlas of the prelimbic region (PrL) a subregion of the prefrontal cortex (PFC) illustrating the area for analysis; (B) Immunohistochemistry (IHC) stain of adolescent PFC and (C) adult PFC showing Arc expression; (D) CORT exposure did not affect Arc expression in the PFC. Adolescent rats displayed an overall greater amount of Arc expression in the PFC. Ø Chronic CORT exposure produces a significant decrease in sucrose intake in adult male rats, which is indicative of anhedonic-like behavior. Ø However, this effect was not observed in adolescent male rats Ø Tissue analysis revealed overall greater Arc expression in adolescent vs. adult male rats across both groups (CORT/H 2 O). Future work will examine other brain regions, such as the nucleus accumbens, and the amygdala. Ø Further research should explore the effects of chronic CORT exposure in adolescence and its potential effects on the emergence of anhedonic-like behavior in adulthood. Exposure Day 0 2 4 6 8 10 12 14 16 18 20 Weights (g) 0 100 200 300 400 500 Adolescent CORT Adult CORT Adolescent Water Adult Water Exposure W C W C Arc positive pixels/mm 2 0 500 1000 1500 2000 2500 3000 Water CORT Adolescents Adults Anhedonic-like behavior emerges following CORT (7 d) in adult rats Anhedonic-like behavior persists following CORT (21 d) in adult rats Anhedonic-like behavior persists following CORT (14 d) in adult rats Adolescent Adult Arc expression is not altered by CORT exposure

Transcript of Stress hormone exposure induces anhedonic-like behavior in adult male rats but not in adolescent...

Page 1: Stress hormone exposure induces anhedonic-like behavior in adult male rats but not in adolescent rats

ACKNOWLEDGEMENTS

Thanks to The Foundation of Hope and NIAAA grant AA019682 to JB and the Bowles Center for Alcohol

Studies for making this work possible

INTRODUCTION

ARC EXPRESSION

CONCLUSIONS

POST 7-D CORT POST 21-D CORT

PROCEDURE

POST 14-D CORT

Stress has been shown to be a major predictor in the onset ofvarious neuropsychological disorders including majordepressive disorder (MDD). A core symptom of MDD isanhedonia or a loss of interest/pleasure in normally rewardingactivities. However little is known about how stress exposureduring the adolescent developmental period affects theemergence of anhedonia and how this differs from stressexposure in adulthood. Using an animal model we havepreviously shown anhedonic-like behavior in male adult ratsfollowing chronic exposure to the stress hormonecorticosterone (CORT). Thus, the aim of this work is to explorethe relationship between CORT exposure and anhedonic-likebehavior as measured by sucrose intake tests in adolescentand adult male rats. Adolescent (PND 28) and adult (PND 70)rats were exposed to CORT (0.3 mg/ml) for 21 days. Sucroseintake tests were conducted weekly to measure anhedonic-likebehavior. Here we show that chronic CORT exposure doesindeed predict a significant decrease in sucrose intake in adultmale rats; however, this effect was not observed in adolescentmale rats. These results suggest that there are underlyingmolecular mechanisms that protect adolescent male rats fromthe development of anhedonic-like behavior following CORTexposure. Immunohistochemical analyses of Arc expression-an immediate early gene and marker for neural plasticity-wereconducted to identify the underlying molecular mechanisms ofthis effect.

Figure 3: SI test conducted following 7 days of CORT and water exposurerevealed a significant decrease in sucrose intake among adult rats exposed toCORT but not water. This effect was not observed in adolescent rats. *p<0.05

Figure 5: SI test conducted following 21 days of CORT and water exposurerevealed a significant decrease in sucrose intake among adult rats exposed toCORT but not water. This effect was not observed in adolescent rats. *p<0.05

Figure 4: SI test conducted following 14 days of CORT and water exposure revealed asignificant decrease in sucrose intake among adult rats exposed to CORT but not water.This effect was not observed in adolescent rats. *p<0.05

Stress hormone exposure induces anhedonic-like behavior in adult male rats but not in adolescent rats.

B. Fortino, V. Agan, A.A. Jaramillo, J. BesheerBowles Center for Alcohol Studies, Department of Psychiatry, University of North Carolina at Chapel Hill

Psychology Department Sponsor: Dr. Charlotte Boettiger

PrL

Post 7-d CORT

Suc

rose

(0.5

% w

/v) I

ntak

e (m

l/kg)

0

5

10

15

20

25WaterCORT

Adolescent Adult

Post 14-d CORT

Sucr

ose

(0.5

% w

/v) I

ntak

e (m

l/kg)

0

5

10

15

20

25WaterCORT

Adolescent Adult

*

Post 21-d CORT

Sucr

ose

(0.5

% w

/v) I

ntak

e (m

l/kg)

0

5

10

15

20

25WaterCORT

Adolescent Adult

*

*

BL SISISI7-d CORT/H2O 14-d CORT/H2O 21-d CORT/H2O

Figure 1: Adolescent (PND 28) and adult (PND 70) male LongEvans rats were given a baseline (BL) sucrose intake (SI) test.Adult and adolescent rats were then given a bottle containing aCORT solution (0.3 mg/ml) or H2O for 21 days. Weekly sucroseintake (SI) tests were conducted

WEIGHTS

A B C

D

Figure 2: Daily average weight of adolescentand adult rats during water and CORTexposure did not differ among age group.

Figure 6: (A) Atlas of the prelimbic region (PrL) a subregion of the prefrontal cortex(PFC) illustrating the area for analysis; (B) Immunohistochemistry (IHC) stain ofadolescent PFC and (C) adult PFC showing Arc expression; (D) CORT exposure didnot affect Arc expression in the PFC. Adolescent rats displayed an overall greateramount of Arc expression in the PFC.

Ø Chronic CORT exposure produces a significant decrease in sucrose intake in adultmale rats, which is indicative of anhedonic-like behavior.

Ø However, this effect was not observed in adolescent male ratsØ Tissue analysis revealed overall greater Arc expression in adolescent vs. adult male

rats across both groups (CORT/H2O). Future work will examine other brain regions,such as the nucleus accumbens, and the amygdala.

Ø Further research should explore the effects of chronic CORT exposure in adolescenceand its potential effects on the emergence of anhedonic-like behavior in adulthood.

Exposure Day0 2 4 6 8 10 12 14 16 18 20 22

Wei

ghts

(g)

0

100

200

300

400

500Adolescent CORTAdult CORTAdolescent WaterAdult Water

ExposureW C W C

Arc

posi

tive

pixe

ls/m

m2

0

500

1000

1500

2000

2500

3000

WaterCORT

Adolescents Adults

Anhedonic-like behavior emerges following CORT (7 d) in adult rats

Anhedonic-like behavior persists following CORT (21 d) in adult rats

Anhedonic-like behavior persists following CORT (14 d) in adult rats

Adolescent Adult

Arc expression is not altered by CORT exposure