Learning Memory Processes Under Stress Conditions

8/12/2019 Learning Memory Processes Under Stress Conditions

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E L S E V I E R Behavioural Brain Research 83 (1997) 71-7 4

BEH VIOUR LBR IN

RESE RCH

R e s e a r c h r e p o r tL e a r n i n g m e m o r y p r o c e s se s u n d e r s tr e ss c o n d i t io n sH i r o s h i K a n e t o *

Department o f Pharmacology, Fac ulty of P harmaceutical Sciences, Nagasaki University, Nagasa ki 852, JapanReceived 8 July 1995; revised 14 No vem ber 1995; accepted 22 Nov emb er 1995

A b s t r a c tU s i n g m i c e , c h a n g e s i n th e l e a r n i n g / m e m o r y p r o c e s s e s u n d e r v a r i o u s s t re s s c o n d i t i o n s w e r e i n v e s t ig a t e d i n o n e - t r i a l s t e p - t h r o u g h

t y p e p a s s i v e a v o i d a n c e l e a r n i n g t a s k . P r e - , p o s t - t r a i n i n g a n d p r e - t e s t f o o t s h o c k ( F S ) - s t r e s s i n d u c e d l o n g - l a s t i n g , a t l e a s t 9 6 h ,f a c i li t a ti o n o f te s t t r i a l l a te n c ie s . P r e - t r a i n i n g p s y c h o l o g i c a l ( P S Y ) - s t r e s s i n d u c e s f a c i l i t a ti o n a n d p r e - t e s t s w i m m i n g ( S W ) - s t r e s sp r o v o k e s i m p a i r m e n t o f te s t t r ia l l a t en c i es . T h e s e e f fe ct s o f F S - , P S Y - a n d S W - s t r e s s a r e a l l d e p e n d e n t o n t h e t i m i n g o f th e i re x p o s u r e a n d d u e t o t h e i r a c u t e e ff ec t. I n t r a p e r i t o n e a l a d m i n i s t r a t i o n o f 1 m g / k g s c o p o l a m i n e 3 0 m i n p r e - t r a i n i n g c a u s e di m p a i r m e n t o f te s t l a te n c i e s i n n a iv e a n d p r e - t e s t F S - s t r e ss e d a n i m a l s b u t f a i le d t o a f fe c t b o t h p r e - a n d p o s t - t r a i n i n g F S - i n d u c e de n h a n c e m e n t . T a k e n a l l t h e s e d a t a t o g e t h e r , i t s e e m s t h a t c h o l i n e r g i c m e c h a n i s m i s p a r t l y i n v o l v e d i n t h e F S - s t r e s s i n d u c e df a c i li t a ti o n o f t e st l a t en c i e s, t h o u g h t h e r e s e a r c h o n t h e c h a n g e s i n A C h l e v e l s a t t h e a c t i o n s i t e in b r a i n a f t er F S - s t r e s s e x p o s u r ei s necessary for a def in i te conc lus ion .Keywords: Learning/memory; Passive avoidance learning; Mouse; Stress; Cholinergic mechanism; Scopolamine

1 IntroductionW e h a v e d e m o n s t r a t e d t h a t f o o t - sh o c k F S ) - , p sy c h o -l o g ic a l P S Y ) - a n d fo r c e d sw i m m i n g S W ) - s t r e s s e x p o -su r e c a n m o d u l a t e t h e l e a r n i n g / m e m o r y p r o c e s se s ,acqui s i t i on , conso l ida t ion , r e t en t ion and re t r i eva l i n ad i ff e re n t w a y , a n d su g g e s t e d t h e i n v o l v e m e n t o f b o t ho p i o i d a n d n o n - o p i o i d m e c h a n i sm s i n t h e p r o c e s se sd e p e n d i n g o n t h e t y p e o f s t re s s [ 4 ] . O n t h e o t h e r h a n d ,a n i m p o r t a n t r o l e o f c h o l i n er g i c sy s t e m i n c o g n i ti v efunc t ion i s we l l r ecognized [1 ,5] . Thus , i n t h i s expe r i -m e n t , t h e c h a n g e s o f l e a r n i n g / m e m o r y p r o c e s se s u n d e rva r ious s t re ss condi t ions were inves t iga t ed in re l a t ion to

t h e i n v o l v e m e n t o f c h o li n e r g ic m e c h a n i sm s .2 Ma terials and methods2.1 . A nim al and exper imenta l condi tions

M a l e m i c e o f t h e d d Y s t r ai n O h t su b o E x p . A n i m a l s,N a g a sa k i , J a p a n ) w e i g h i n g 1 8 - 2 0 g w e r e p u r c h a se d a n dhou sed in 42 26 x 15 cm p las t i c cages w i th f ree accessto food and w a te r unde r a na tura l d ay /n igh t cyc le . A l l

e x p e r i m e n t s w e r e c a r r i ed o u t b e t w e e n 9 : 0 0 a .m . a n d3 : 00 p .m. to min imize d iurna l va r i a t ion .2.2. Ex posu re to s tress

F o o t sh o c k F S ) - st r es s : T h e c o m m u n i c a t i o n b o x30 x 30 x 30 c rn) which wa s d iv ided in to 9 com par tm ent s10 x 10 x 30 c rn) w i th t ranspa r en t p l a s t i c wa l l s was used .I n e sc a p a b l e a n d u n s i g n a l e d e l e ct r ic f o o t sh o c k F S ,2 mA, 1 s dura t ion , 0 .2 Hz) dura t ion) was de l ive red for5 min th rou gh the f loor g r id . P sycholog ica l PSY)-s t re ss :T h e s a m e b o x w a s u se d . P l a s t i c p l a t e s w e r e p l a c e d o nt h e g r id s o f 5 c o m p a r t m e n t s t o p r e v e n t t h e a n i m a l s f r o mr e c e i v i n g d i r e c t sh o c k , b u t t h e y w e r e e x p o se d t o P S Y -s t re s s b y w a t c h i n g a n d h e a r i n g t h e s t ru g g l e, j u m p i n gand voca l i za t ion o f t he an ima l rece iv ing FS in thea d j a c e n t c o m p a r t m e n t s , f o r 5 m i n . S w im m i n g S W ) -s t re ss : Mice were forced to swim in a wa te r ba th ,4 0 L ) x 3 5 W ) x 2 0 H ) c m , 1 5 c m o f w a t e r d e p t h a t 2 0 Cfor 5 rain. A f t e r rem oving the an ima l f ro m w a te r re turne dt o t h e h o m e c a g e b e f o r e su b se q u e n t t e s ti n g .2.3. Step-th roug h type pass ive avoidance learning tes t

* Corresponding author. T el.: (+ 81 ) 958-4%1111, Ext. 2538; Fax: {+ 81 )958-44~4248. T h e a p p a r a t u s c o n s i s t e d o f a n i l lu m i n a t e d a n d a d a r kcom par tm ent each 4 x 13 x 19 c rn) ad jo in ing each o the r0166-4328/97/ 17.00 Copyright 1997 Elsevier Science B.V. All rights reservedPII SO 1 6 6 - 4 3 2 8 ( 9 6 ) 0 0 0 9 6 - 4


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72 11. Kaneto/Behavioural Brain Research 83 (1997) 71-7 4

t h rou gh a sma l l ga t e (3 cm in d i amete r ) w i th a g r idf loor . On the t ra in ing t r i a l , t he an ima l was p l aced in thei l lu m i n a t e d c o m p a r t m e n t f a c in g a w a y f r o m t h e d a r kc o m p a r t m e n t . W h e n t h e a n i m a l e n t e r e d i n t o t h e d a r kcom par tm ent , an e l ec t r ic shock (ES ; 0 .6 mA ) was de l iv -e red th rough the gr id f loor un t i l t he an ima l re turned tothe i l lumina ted com par tm ent . A t t he t e s t tr ia l, 24 h a f t e rthe t ra in ing sess ion un less o the rwise spec i fi ed , t he an im a lp l a c e d i n t h e i l l u m i n a t e d c o m p a r t m e n t a n d i t s l a t e n c yt o e n t er t h e d a r k c o m p a r t m e n t ( m a x i m u m 6 0 0 s ) w a sm e a su r e d .

T h e e f fe c t o f s tr e s s e x p o su r e o n l e a r n i n g / m e m o r yprocesses were t e s t ed a t 3 d i f fe ren t s t ages . (1 ) Pre-training: Animal s were exposed to s t re ss and re t ,~ .nedto the i r home cages un t i l t he t ra in ing t r i a l . (2 j Pos t -training: Mice were exposed to s t re ss a t va r ious in t e rva l sa f t e r t he t ra in ing t r i a l and re turned to the i r home cages .(3) Pre-test: St ress was de l ive red a t d i f fe ren t t imeintervals before the test t r ia l .

2.4. S tat is t ica l analysisD a t a a r e e x p r e s se d a s m e d i a n s a n d i n t e r q u a r t i l e

ranges ( s ) . A l l da t a were ana lyzed by the K ruska l -W al l i sn o n - p a r a m e t r i c o n e - w a y a n a ly s i s o f v a r i an c e , a n d su b se -q u e n t l y , p o s t - h o c t e s t s w e r e p e r f o r m e d w i t h t h e t w o -t a i l ed Mann-Whi tney U- te s t . In s t a t i s t i ca l eva lua t ions ,P < 0 . 0 5 w a s u se d a s t h e c r i t e r i o n f o r s t a t i s t i c a lsignificance.

600

400

200

= 0

6 0 0 -

4 0 0 -

200 -

0 -

C o n t r o l( n o n - s t r e s s e d )

Ir . ~

P r e - t r a i n i n gI

T. . J

//1P o s t - t r a i n i n g

I ~ 1Tr

7 Z

Pre - t e s t

///]////

//////

964 48 72 96 24 48 72T r a i n i n g - te s t i n t e r v a l ( h r )

F i g . 1 . D u ra t i o n o f t h e e n h a n c e m e n t o f t h e t e s t l at e n c ie s i n d u c e d b ypre- , post - t ra in ing and pre-test FS-st ress . Test was performed a t 24(o p e n c o l u mn ) , 4 8 (d a rk g re y c o l u mn ) , 7 2 ( l i g h t g rey c o l u mn ) a n d 9 6(h a r t c h e d c o l u mn ) h a f te r tr a i n i n g tr i a l. + P < 0 .0 5 , + P < 0 .0 1 , c o m -p a re d w i t h t h e v a l u e a t 2 4 h a f t e r t r a i n i n g i n n o n -s t re s se d c o n t ro lg ro u p . * * P< 0 .0 1 , c o mp a re d w i t h t h e c o n t ro l g ro u p a t c o r re sp o n d -ing t ime.

3 . R e s u l t sA s s h o w n i n F ig . 1 n o n - s t r e s se d c o n t r o l a n i m a l s su b -

j e t t e d t o o n e t r i a l i n t h e p a s s i v e a v o i d a n c e l e a r n i n gp a r a d i g m sh o w e d a n e n h a n c e d t e s t l a te n c ie s 2 4 h a f t e rt ra in ing tha t dec reased t ime-dependent ly in the fo l lowingdays a nd a t 72 and 96 h a f t e r t r a in ing the l a t encyre turned to the cont ro l l eve l . In cont ra s t , p re - , pos t -t ra in ing and pre - t e s t FS-s t re ss exposure re su l t ed ine n h a n c e d t e s t l a te n c i es c o m p a r e d t o n o n - s t r e s se d c o n t r o lg r o u p , sh o w i n g a n i n c id e n c e o f m a x i m u m r e t e n t io nlatencies o f 600 s that lasted a t least for 96 h. In a l lcases , t r a in ing l a t enc ie s were no t a f fec t ed by s t re ssexpo sure (FS : 16 , 11-24; PSY : 20 , 11-25; SW : 20 , 13-22) .

I n c o n t r a s t , a s r e p o r t e d p r e v i o u s l y [ 4 1 , p r e - t r a i n i n gP S Y - s t r e s s i n d u c e d e n h a n c e m e n t a n d p o s t - t r a i n i n gSW -st re ss evoke d impa i rm ent o f t he t e s t t r i al l a t enc ie sa t 24 h a f t e r t r a in ing t r i a l, bu t pos t - t ra in ing and pre - t e s tPSY-s t re ss and pre - t ra in ing and pre - t e s t SW-st re ss fa i l edto a f fec t the t e s t t r i a l l a t enc ie s . The se e f fec ts i nduced byP S Y - a n d S W - s t r e s s w e r e r a p i d l y d i m i n i sh e d a n dre turne d to the con t ro l l eve l by 48 h (F ig . 2) .

Pro-training Post-trainingPSY-st ress SW-st ress~ . 600

l , / l lo C o n t 2 4 4 8 7 2 9 6 C o n t 2 4 4 8 7 2 9 6

Tr ain in g- tes t in terval (hr)F i g . 2. D u ra t i o n o f t h e e n h a n c i n g e f fe c t o f p re - t ra i n i n g PSY -s t re s s a n dimp ai ring effec t o f post - t ra in ing SW-st ress . Test was perform ed a t 24 ,4 8 , 7 2 a n d 9 6 h a f t e r tr a i n i n g t ri al . * P < 0 .0 5 , c o mp a re d w i t h t h e c o n -t ro l g ro u p .

3.1. Tim e dependency o f the s tress-induced ef fectF S - s t r e s s e x p o su r e 3 0 m i n p r e - t r a i n i n g p r o d u c e d a

ma rked inc rease of re t en t ion l a t enc ie s a t t he t e s t t r i alt h a t d e c r e a se d g r a d u a l l y a n d d i s a p p e a r e d w h e n t h ein t e rva l be tween FS-s t re ss exposure and t ra in ing t r i a l


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11. Kaneto/Behavioural Brain Research 83 (199 7) 71-7 4 73

w a s 1 a n d 2 h . S i m i l a r r e s u l t s w e re o b t a i n e d b y p o s t -t ra in ing and p re- tes t expo sure to FS-s t res s F ig . 3 ) .

Th e e f fe c ts o f e x p o s u re t o p r e - t r a i n i n g P S Y -s tr e s s a n dp o s t - t r a i n i n g S W -s t r e ss o n t h e t e s t l a te n c i e s d e t e rm i n e da t 2 4 h a f t e r tr a i n i n g w e re a l s o t i m e -d e p e n d e n t . W h e nt h e i n t e rv a l b e t w e e n s t r e s s a n d t r a i n i n g t r i a l w a s m o ret h a n 1 h t h e e n h a n c i n g a n d i m p a i r i n g e f f e ct s w e re l o s tFig. 4).3.2. Ef fect o f FS-stress on scopolamine-induced amnesicef fect

In t r a p e r i t o n e a l i n j e c ti o n o f 1 m g / k g s c o p o l a m i n eS c o p ) 3 0 m i n b e fo re t r a i n i n g r e s u l t e d i n a p ro fo u n d

decrease o f t es t t r i a l l a tenc ies in non-s t res sed con t ro lan imals . H owe ver , fac i l it a ted tes t l a tenc ies f rom an im alss u b j e c t e d t o p r e - a n d p o s t - t r a i n i n g F S - s t r e s s w e re n o taf fec ted by p re- t ra in in g Scop , ind ica t ing tha t Scop

P r e - P o s t -t r a i n i n g t r a i n i n g P r e - t e s t600 -

4 0 0

m 0 1 0.5 1 2 0.5 1 2S t r e s s (F S ) - t r a i n i n g i n t e r v a l ( h r )

F i g . 3 . T i me d e p e n d e n c y o f t h e FS-s t re s s i n d u c e d fa c i l it a t i o n o f t h e t e s tla tencies on the in terval o f st ress ex posur e and t ra in ing t r ia l . Mice weree x p o se d t o FS-s t re s s 3 0 ra in , 1 a n d 2 h p re - t ra in i n g , p o s t - t r a i n i n g a n dp re - t es t . Te s t w a s p e r fo rme d 2 4 h a f t e r t r a i n in g t r i a l. * * P< 0 .0 1 , c o m-p a re d w i t h t h e c o n t ro l (C o n t . ) g ro u p .

P r e - t r a i n i n gP S Y - s t r e s s6 0 0 - *

~ 4 0 0 -

~ 200

m 0

P o s t - t r n i n i n gS W - s t r e s s

C o n t 0 . 5 1 2 C o n t 0 . 5 1 2S t r e s s - t r a i n i n g i n t e r v a l ( h r )

F i g . 4 . T i me d e p e n d e n c y o f t h e PSY -s t re s s i n d u c e d fa c i l i t a ti o n a n d t h eSw - i n d u c e d i mp a i rme n t o f t h e t e s t l a t e n c ie s o n t h e i n t e rv a l o f s t re s se x p o su re a n d t r a i n i n g t r i a l . M i c e w e re e x p o se d t o p re - t ra i n i n g PSY -st ress and to post - t ra in ing SW -st ress a t the t ime in terval o f 30 ra in , 1and 2 h betw een s t ress exposu re a nd t ra in ing t r ia l , respect ive ly.* P < 0 .0 5 , c o m p a re d w i t h re sp e c t iv e c o n t ro l (C o n t . ) g ro u p .

i n d u c e d a m n e s i c e ff e c t w a s b l o c k e d b y s t re s s e x p o s u re .In con t ra s t , p re - tes t FS-s t res s fa il ed to b lock the a mn es icef fec t o f Scop F ig . 5 ) . W herea s FS-s t res s exp osed 30m i n p r e - t r a i n i n g b l o c k e d t h e a m n e s i c e f f ec t o f S c o p , 1a n d 2 h p r e - t r a i n i n g F S - s t r e ss d i d n o t a f fe c t t h e a m n e s i ceffect of Scop Fig . 6).

4 . D i s c u s s i o n

Th e p re s e n t s t u d y h a s b e e n c a r r i e d o u t u s i n g m i c e ,s ince mice t ra ined on ly once es tab l i sh a long- las t ingm e m o ry t h a t l a st s a t l e a st 2 4 h i n s t e p - t h ro u g h t y p ep a s si v e a v o i d a n c e l e a rn i n g t a s k . W e c o n f i rm e d o u r p r e v i -ous da ta 1 -5] tha t t es t t r i a l la tenc ies a t 24 h a f te r t ra in ingt r i a l were s ign i f i can t ly p ro longed in mice exposed to

Pre - Po s t - Pre-testtraning training6 0 0 7

400 I

~ 2 0 0 ' * *

m 0non - stressed FS - stressed

Fig . 5 . Effec t o f FS-st ress on Scop -induce d am nesic effec t. Scop( 1 mg / k g ) w a s a d m i n i s t e re d 3 0 ra i n b e fo re t r a in i n g . FS -s t re ss w a s d e l i v -ered 30 ra in pre- , post - t ra in ing and 30 ra in pre-test . Test t r ia l was done24 h after t ra in ing t r ia l . Cont r o l (g iven sal ine , open co lumn s) and Sc op-t re a t e d (b la c k c o l u mn s) g ro u p . * * P< 0 .0 1 , c o mp a re d w i t h n o n -st re s se dc o n t ro l g ro u p . ~ P< 0 .0 1 , c o mp a re d w i t h t h e c o r re sp o n d i n g s t re s se dgroup g iven sa l ine .

, - , 6 O O

~ 4 o o

0

Pre-training FS-stress

n o n stressed 0 . 5 ~ 1Stre ss- t ra in ing in terval (hr)

Fig . 6 . Effec t o f p re-t ra in ing exp osure to FS -st ress a t d i fferen t t im ei n t e rv a l s o n t h e Sc o p - i n d u c e d a mn e s i c e f fe c t . M i c e w e re e x p o se d t oFS-s t re s s 3 0 mi n , 1 a n d 2 h b e fo re t r a in i n g , a n d S t o p w a s g i v e n 3 0 ra i npre-t ra in ing . Test tr ia l was measu d 24 h after t ra in ing . Cont r o l (g ivensal ine , open co lumns} and Scop-t rea ted (b lack co lumns} group .* P< 0 .0 5 , * * P< 0 .O 1 , c o mp a re d w i t h n o n -s t re s se d c o n t ro l g ro u p .##P


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74 1-1. Kaneto/Behavioural B rain Research 83 (19 97) 71-7 4FSost ress p re- t ra in ing pos t . t ra in ing and p re- tes t ind i -c a t i n g t h a t m e m o ry fo rm i n g p ro c es s e s a c q u i s it i o n c o n -so l ida t ion re ten t io n and re t r i eva l mig h t be fac i l i t a tedby s t ress exposure How ever the e f fect s o f s t resses wered i f f e re n t e a c h o t h e r d e p e n d i n g o n t h e i r t y p e a n d p re -t r a i n i n g P S Y-s t r e s s e x p o s u re a l s o e n h a n c e d t h e t e s tl a tenc ies a t 24 h a f te r the t ra in ing bu t fa i l ed to mo d i fythe tes t l a tenc ies by pos t - t ra in ing o r p re- tes t exposure .In c o n t r a s t S W -s t r e ss p ro d u c e d n o e f f e c t b y p re - t r a i n i n ga n d p re - t e st e x p o s u re b u t i m p a i r e d t h e t e s t la t e n c ie s b ypos t - t ra in ing exposure .

The fac t tha t p re- pos t - t ra in ing and p re- tes t FS-s t ressinduce d fac i l i t a t ion was long- las t ing a t l eas t 96 h bu tt h e e n h a n c e m e n t c a u s e d b y p re - t ra i n i n g P S Y-s t r e ss a n dt h e i m p a i rm e n t i n d u c e d b y p o s t - t r a i n i n g S W -s t r e s s a t24 h a f te r the t ra in ing t r i a l d i sappeared in the fo l lowingd a y s m a y s u g g e st t h e i m p l i c a t i o n o f t h e d i f f e r e nt m e c h a -n i s m s a m o n g 3 t y p e s o f s tr e ss e s fo r t h e i r p ro d u c t i o n .On t h e o t h e r h a n d t h e f a c il i ta t i o n i n d u c e d b y F S - s t r e s sa p p l i e d a t 3 d i f f e re n t s t a ge s o f l e a rn i n g / m e m o ry p ro -c e s se s a n d p re - t r a i n i n g P S Y-s tr e s s a n d i m p a i rm e n tc a u s e d b y p o s t - t r a i n i n g S W -s t r e ss a r e d u e t o t h e i r a c u t eeffec t sugges t ing tha t the in te rva l be tween s t ress expo-su re and t ra in ing t ra i l a re c r i t i ca l fac to r fo r the i rp ro d u c t i o n .

T h e i n v o l v e m e n t o f c h o l in e rg i c m e c h a n i s m i n t h ep rocess o f fac i l i t a t ion induc ed by FS-s t ress was inves t i -g a t e d s i nc e t h e re h a v e b e e n m a n y r e p o r t s t h a t g i v ee v i d e n c e o f t h e i m p a i r i n g e f fe c ts o f c o g n i t i o n o f s y s te m i -c a l ly a d m i n i s t e r e d a n t i m u s c a r i n i c a g e n ts s u c h a s s c o p o l -a m i n e [1 3 ] a n d m o re o v e r t h e e ss e n ti a l r o l e o fc h o li n e rg i c m e c h a n i s m i n a n u m b e r o f l e a r n i n g / m e m o r yp ra d i grn s h a v e b e e n s u g g e s t e d [2 5 -7 ] . I n t h is e x p e r i-m e n t we fo u n d t h a t F S - s t r e ss i n d u c e d le a rn i n g e n h a n c e -m e n t l a st e d a t l e a st 96 h i n d i c a t i n g t h a t A C h - i n d u c e dchan ges o f exc i tab i l i ty can b e long- las t ing and causes am e c h a n i s m o f c e n t r a l p l a st ic i ty . I t h a s b e e n s u g g e s t e dtha t FS-s t ress may increase the ACh leve l s in the b ra inand h ighe r level s o f AC h w ou ld incre ase synap t ic e f fec-t iveness o f the neura l c i rcu i t con t ro l l ing re ten t ion la ten -c ie s p r e s u m a b l y r e g u l a t e d t h ro u g h m u s c a r i n i c r e c e p t o rs .Th is poss ib i li ty i s supp or ted by sys temic adm in is t ra t io n

o f a s in g l e 1 m g / k g S t o p c a u s i n g a p ro fo u n d a m n e s i ce f fe c t t h a t c o m p l e t e l y d i s a p p e a re d b y 3 0 m i n p re - a n dpos t - t ra in ing FS-s t ress sugges t ing tha t incre ased level so f A C h i n d u c e d b y F S - e x p o s u re w o u l d c o m p e t e w i the x o g e n o u s l y a d m i n i s t e r e d S c o p fo r m u s c a r i n i c b i n d i n gs h o wi n g a b l o c k i n g o f S c o p - i n d u c e d a m n e s i c e ff e c t a n da s u s t a in e d e n h a n c e m e n t o f t e st l a t en c ie s . Ho we v e rexpo sure to FS -s t ress 30 min befo re t es t fa i led to enha ncetes t l a tenc ies in an imals g iven p re- t ra in ing Scop ind ica t -i n g t h a t S c o p a n t a g o n i s m o f m u s c a r i n i c r e c e p t o r s be fo ret r a i n in g w o u l d b l o c k t h e fo rm a t i o n o f t h e c e n t r a l c ir c u i trespons ib le fo r the in duct io n o f fac i li t a t ion o f tes t l a ten -c ies . One and 2 h p re- t ra in ing FS-exposure d id no t e l i c i ts i gn i fi c a n t e n h a n c e m e n t o f t e s t l a te n c i e s c o m p a re d w i t ht h a t o f n o n - s tr e s s e d c o n t ro l g ro u p . F a i l u r e t o a c t i v a t e along- te rm fac i l i t a t ion p rocess in an imals exposed 1 o r2 h befo re tra in ing m ay be as wel l due to th e p rogress ivedecrease o f AC h leve ls a t the ac t ion s i tes and b lock ingeffec t o f p re- tes t Scop a l so sugges t s the poss ib i l ity .T i m i n g o f s t re s s e x p o s u re a n d AC h p h a rm a c o k i n e t i c sa p p e a r t o b e k e y e l e m e n t s i n t h is p ro c e s s b u t fu r t h e rr e s e a rc h o n t h e p ro b l e m i s n e e d e d t o r e a c h a d e f i n i t econclus ion .

eferences

El '] F ibiger , H.C. , Cen tra l cholinergic systems an d mem ory. In S q u i r eL.R. an d L inde nlau b, E. (Eds. ) The Biology of Memory. Sc ha t -tauer-Verlag, Stut tga r t , New York, 1989, pp. 381-426.[2. ] G lick, S.D. an d Z imm emb vrg, B., Amnesic effec ts of scopolam ine .Behav. Biol., 7 (1972) 245-254.1 3] I zquie rdo , I ., M e c ha nism of a c t ion of s c opola m ine a s a n a m ne sic.Trends PharmacoL Sci., l0 (1989) 175-177.r4. ] Jodar , L. , Takah ashi , M . and Kan eto, H. , Effec ts of foot-shock- ,psychologica l- and swimming-stress o n the learning an d mem oryprocesses: Invo lvem ent of opioidergic pa thways. Jpn. 3. Pharma-col., 67 (1995) 143-147.[51 Ka m e y a m a , T ., Na be shim a , T . a nd Nod a , Y . , Chol ine rg ic m o d u -l a t i o n of memory for s tep-down passive avoidance task in mice .Res. Commun. PsychoL Psychiat. Behav., 11 (1986) 193-215.~6] Rush, D.K. , Reversal of scopolamine-inducext amn esia of pass ivea voida nc e by pre - a nd pos t - t r a in ing na loxone . Psychopharmacol-ogy, 100 (1986) 27-30.17] Rush , D .K . a nd S t r e it , K . , Me m ory m odu la t ion wi th pe riphe ra l lyact ing cholinergic drugs . Psychopharmacology, 106 (199t )375-382.

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