1978 - persinger & fiss - pharmacology, biochemistry & behavior - mesenteric mast cell degranulation...

7/30/2019 1978 - Persinger & Fiss - Pharmacology, Biochemistry & Behavior - Mesenteric Mast Cell Degranulation is Not Esse

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Pharmacology Biochemistry & Behavior, Vol. 9, pp. 725-730. Printed in the U.S.A.

M e s e n t e r i c M a s t C e l l D e g r a n u l a t i o n i s N o tE s s e n t i a l F o r C o n d i t i o n e d T a s t e A v e r s i o n

M I C H A E L A . P E R S I N G E R A N D T E R R Y B . F I S S 2Behavioral Neurobiology Laboratory, Depart ment o f Psychology, Laurentian University, Sudbury, Ontario,

Canada P3E 2C6( R e c e i v e d 1 0 J u l y 1 9 7 8 )

P E R S I N G E R , M . A . A N D T . B . F I S S . Mesenteric mast cell degranulation is not essential or conditioned taste aversion.PHA RM AC. BIOCH EM. BEH AV. 9(6) 725--730, 1978. - -The pos s ib l e ro l e of mesenter ic mas t ce l l degranula t ion as t hemedia tor of t he in i t i a l UCS ef f ec t s in t he complex s equ ences l eading to condi t i oned t as t e aver s ion (CTA) was s tudied . BothLiC1 and C ompound 48/80, a potent mas t ce l l degranula tor , produced CT A to 10% sucrose . W hereas t he Compo und 48/80groups d i sp l aye d mass ive mas t ce l l degranula t ion , ne i ther the LiC1 t r ea t ed nor s a l ine cont ro l groups dem ons t r a t ed anyhi s to logica lly de t erminable a l t e r a t ions . Adm ini s t ra t i on of t he ant ih i s t amine chlorpheni r amine a t dosages known to b lockradia t ion- induced CTA b efore t he sucrose C S-UCS pai r ings d id not b lock e i ther L iCI- or Com pound 48/80-induced C TA;the ant ih i s t amine ac tual ly f ac i l it a t ed the av er s ion . How ever , pr e t r ea tment wi th the ant ih i s tamine d id not a l t e r m esenter i cmas t ce l l morphology.Comp ound 48/80 Mas t ce l l s Mesen tery Condi t i oned t as t e aver s ion Rat L i th ium chlor ideAnt ih i s t amine

T H E C E L L U L A R m e d i a t o r o f c o n d i ti o n e d t a st e a v e rs i on( C T A ) b e t w e e n i n t r a p e r it o n e a l in j e c t io n s o r w h o l e b o d y a p -p l i c a ti o n s ( io n i z in g ra d i a t io n ) o f t h e U C S a n d t h e a c t u a l C N Sp r o c e s s i s n o t c l e a r . G a r c i a [ 6 ] s p e c u l a t e d t h a t C T A i n d u c i n ga g e n t s m a y a l l p r o d u c e s o m e g e n e r a l v i s c e r a l m a l a is e o r i ll -n e s s . A l t h o u g h m a n y C T A i n d u c i n g a g e n t s , s u c h a s c y -c l o p h o s p h a m i d e , a p o m o r p h i n e a n d l i t h i u m c h l o r i d e ( L i C I )h a v e b e e n r e p o r t e d t o e v o k e o v e r t s y m p t o m s o f " s i c k n e s s , "C T A - e l i c i ti n g d o s e s o f i o n i zi n g r a d ia t i o n d o n o t a p p e a r t o b ea s s o c i a t e d w i t h c l e a r s i g n s o f s i c k n e s s [ 6 ]. O t h e r d r u g s , s u c ha s s o d i u m p e n t o b a r b i t a l d o n o t p r o d u c e o b v i o u s s i g n s o ft o x i c i t y i n r a t s b u t s t i l l e l i c i t C T A [ 1] .T h e c e l l u la r m e d i a t o r o f C T A f o l lo w i n g a b d o m i n a l i n t r o -d u c t i o n o f a p p r o p r i a t e s t i m u li s h o u l d d i s p l a y a g r a d e d c a -p a c i t y o f re s p o n s e t o t h e v a r i e t y o f C T A a g e n t s s u c h t h a t" s i c k n e s s " i s m o r e c o r r e l a t i v e to s e c o n d a r y f a c t o r s r a t h e rt h a n t h e s o u r c e o f t h e e f f e c t. O n e p o s s i b l e c a n d i d a t e f o r t h ec y t o l o g i c a l m e d i a t o r o f C T A a g e n t s i s th e m a s t c e l l (M C ) ,s p e c i fi c a l ly m e s e n t e r i c m a s t c e l ls . S i n c e t h e m e s e n t e r y c a r -r i e s b l o o d v e s s e l s , l y m p h a t i c s a n d n e r v e s t o ( a n d f r o m ) v i s -c e r a l o r g a n s , M C s w i t h i n t h i s m a t r i x a r e i n a s t r a t e g i c p o s i -t i o n t o i n f lu e n c e a v a r i e t y o f p h y s i o l o g i c a l c h e m i c a l r e a c -t i o n s .M C s c o n t a i n a s t o r e h o u s e o f b i o p o t e n t m a t e r i a l s i n c l u d in gh i s t a m i n e , h e p a r i n , p r o t e i n p o l y s a c c h a r i d e s , p o l y p e p t i d e s ,s e r o t o n i n , a n d d o p a m i n e [ 1 0 ] . T h e s e s u b s t a n c e s a r e c o n -t a i n e d w i t h in c y t o p l a s m i c g r a n u l e s t h a t c a n b e r e l e a s e d i n a ne x p l o s i v e o r in a g r a d u a l m a n n e r b y e i t h e r a s m a l l p o r t i o n o ra l l o f a M C p o p u l a t i o n f o l l o w in g c o n t a c t w i t h a v a s t n u m b e r

o f s u b s t a n c e s i n c lu d i n g i o n iz i n g ra d i a t i o n , m a n y o f t h e C T Ac h e m i c a l s a n d e v e n d i s t i ll e d w a t e r [ 1 I ] . O n c e r e l e a s e d i n t oi n t e r s t i ti a l f l u i d s , M C c o m p o u n d s c a n c o n t r i b u t e t o l o c a lv a s o d i l a t i o n , h e m a t o l o g i c a l c h a n g e s , i n i t i a t i o n o f t i s s u el e u k o c y t i c a c t i v i ty a n d i m m u n e - r e l a t e d r e s p o n s e s [1 0]. M C sa r e m o r e w e l l k n o w n a t a s y s t e m i c o r o r g a n i s m i c l e v e l f o rt h e i r c o n t r ib u t i o n t o a n a p h y l a c t i c s h o c k .S e v e r a l l i n e s o f e v i d e n c e i m p l y t h e c o n t r i b u t i o n o f M Cd e g r a n u l a t i o n t o C T A : ( 1) A g e n t s k n o w n t o e l i ci t C T A a r ee i t h e r e s t a b l i sh e d o r l i k e ly p e r i t o n e a l / m e s e n t e r i c M C d e -g r a n u l a t o r s [ 1 1 ]. ( 2 ) I o n i z i n g r a d i a t i o n , a f r e q u e n t l y u s e dU C S i n C T A s t u d i e s [ 6 ,8 ] i n i t i a te s m a s s i v e d e g r a n u l a t i o n i na b d o m i n a l M C p o p u l a t i o n s [ 11 ]. A n t i h i s ta m i n e s c a n n o t o n l yp r e v e n t r a d i a t i o n - i n d u c e d M C d e g r a n u l a t i o n [ 12 ] b u t a l s ob l o c k C T A t o s a c c h a r i n p a i r e d w i t h i o n i z i n g r a d i a t i o n [8 ]. ( 3 )A C T H a n d r e l a t e d st r u c t u re s c a n b e d e g r a n u l a t o r s o f a b d o m -i n a l M C s [ 11 ]; p l a s m a c o r t i c o s t e r o n e l e v e l s h a v e b e e nd e m o n s t r a t e d t o b e i n d i c e s o f t h e s t r e n g t h o f C T A [ 13 ]. ( 4 )T h e r a t w h i c h h a s b e e n c a l l e d a m a s t c e l l a n i m a l [ 4] b e c a u s eo f t h e l a rg e c o n c e n t r a t io n s o f t h e s e c e l l s t h r o u g h o u t t h e c o n -n e c t i v e t i ss u e m a t r i x , i s e s p e c i a ll y p r o n e t o C T A p a r a d i g m s ,e . g . , b a i t s h y n e s s .T o t e s t th e M C h y p o t h e s i s , e x p e r i m e n t s w e r e d e s i g n e d t oa n s w e r t h e f o l l o w i n g p r e d i c t io n s . I f m e s e n t e r i c M C s a r e a s -s o c i a t e d w i th C T A , t h e n t h e p a i r i n g o f t h e C S s u c r o s e w i t ht h e U C S C o m p o u n d 4 8 /8 0 [1 1] , a w e l l k n o w n M C d e -g r a n u l a t o r , s h o u ld p r o d u c e C T A t o s u c r o s e c o m p a r a b l e t ou s u a l e x p e r i m e n t a l d o s a g e s o f L i C I o r i o n i z i n g ra d i a t io n .P r e t r e a t m e n t w i t h t h e a n t i h i s t a m i n e c h l o r p h e n i r a m i n e

~This s tudy was supp or t ed in par t by Canadian N at ional Research Grant Nu mbe r A0291.2Now at: Depa r tment of Psychology, York Univer s i ty , Downsview, Ontar io , Canada.

C o p y r i g h t 1 97 8 A N K H O I n t e r n a t i o n a l I n c . - - 0 0 9 1 - 3 0 5 7 /7 8 / 1 2 0 7 2 5 - 06 5 0 1 . 1 0 / 0


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726 PERS INGE R AND FISS

20 _

15_E

I0_

Basel ine H20

[ ] Phys io log io l sa li ne ( I 0 m l / k g )[ :~ 0.15 M L i th ium chlor ide ( IOrnl / kg )[ ] 2 m g / k g C 4 8 1 8 0 ( lO m l / k g) '[ ] 2 m g / k g C 4 8 1 8 0 ( I m l / l ~ )

l r T

Initial SucroseTreatment

Recovery H20

T

SucroSe Test

FIG. 1. Mean water consumption during baseline and recovery daysand mean IIF/~ w/v) sucrose consumption during initial sucrose andsucrose test days for groups of rats that were injected after the firstsucrose presentation with either physiological saline, 0.15 M lithiumchloride, or one of two volumes of Compound 48/80. Vertical barsindicate standard errors of the mean.

maleate at dosages (20 mg/kg) sufficient to block radiationinduced aversion to saccharin (8) should block CTA to suc-rose induced by C 48/80 but not by LiCI (replication of [8]).(Implicitly, this argument demands that some dosage orsome type of antihi stamine should be able ultimately to blockLiCl-induced CTA.) If MC degran ulation contributes to CTAin general, then the differential effects of the antihistamineupon the CTA producing properties of different UCSs shouldreflect the degree of preventative degranulation. Conse-quently , both LiCl-induced and C 48/80-induced CTA shouldbe associated with MC degranulati on while pretreatmentwith chlorpheniramine should prevent CTA to C 48/80 aswell as MC degran ulation but not eliminate CTA or degranu-lation to LiC1.

EXPERIMENT 1M E T H O D

In two separate test runs, 28 naive male 300 day old(600 _ 50 g) albino Wistar rats were removed from grouphousing, placed in single cages, main tained on a 23.7 hrwater deprivation schedule and exposed to a typical CTAparadigm [9]. For 5 days, they were given access to water for20 min per day in their home cages. On Day 6 (conditioningday), the rats were allowed to drink 10% (w/v) sucrose for 20min and then rando mly allocated to one of four groups (n=7each). Within 5 to 15 min, the rats were injected IP with oneof four subs tan ces : (1) 10 cc/kg of 0.15 M LiCI, (2) 10 cc/kg of2 mg/10 cc of C 48/80 in physiolo gical saline, (3) 1 cc/kg of 2mg/cc of C 48/80 in physiolo gical saline, o r (4) 10 cc/kg ofphysiological saline. Due to injection difficulties, one rat inthe physiological saline group was eliminated from the study.On Days 7 and 8 (recovery days), the rats were allowedwater on ly for 20 min per day. On Day 9 (test day), rats were

allowed 20 min access to the 10% sucrose solutions. All so-lutions were delivered in 1 ml graduated 100 ml drinkingbottles. The following colony conditions existed for all ex-periments: LD cycle: 12:12; temperature: 21 +- IC; relativehumidity: 45 _+ 5%; background noise: 70 _+ 2 dB. All dataanalyses were completed by com puter using SPSS packages;sample analysis were checked manually.R E S U L T S

The means and standard errors for water intake (in ml)during baseline and recovery days and for sucrose intakes (inml) during conditioni ng and test days are shown in Fig. 1.One way analyses of variance between groups demonstratedno significant differences (F 0. 05) in fluid consu mp-tion during baseline, conditioning or recovery days. How-ever, highly sig nificant (F(3,23) = 34.66, p


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tu i

L O O ~t~ JIt .la J

0 . 5 iIz

N H

T

/ 3 1L i C l 2 . 0( CompoundTREATM ENT

1 .0 0 . 6 0 . 2 ~ 0 , 0 2i4 8 / 8 0 ( r a g k g )

FIG. 2 . M ean sucrose pr ef er ence s co res for groups (n=6/group) ofr a t s g iven d i f f er ent dosages of Com pound 48/80 ( in 2 c c /kg volumes ) ,10 cc/kg o f 0.15 M LiC1, phy siological sal ine (2 cc/kg): S, o r not r ea tment (non-handled: NH ) . V er t i ca l bar s i ndica t e s t andard er ror so f t h e m e a n .

g r o u p s w a s s i g n i f i c a n t , F ( 7 ,4 0 ) = 1 1 .9 7 , p < 0 . 0 0 1 . D u n c a n ' sm u l t i p le r a n g e t e s ts s e t a t p < 0 . 0 5 d e m o n s t r a t e d t h a t t h e L i C Ia n d 2 m g / k g C 4 8 /8 0 g r o u p s w e r e d i f f e r e n t f r o m a l l o t h e rg r o u p s a n d t h a t t h e 1 m g / k g C 4 8 /8 0 g r o u p w a s s i g n i f i c a n t lyd i f fe r e n t f r o m b o t h t h e f o r m e r t w o g r o u p s a n d t h e o t h e rg r o u p s . A l l o t h e r g r o u p d i f f e r e n c e s w e r e n o t s ig n i f i c a n ts t a t i s t i c a l l y .E X P E R I M E N T 3

O n t h e b a s i s o f th e a b o v e r e s u l ts , t h e 1 m g / k g d o s a g e o f C4 8 /8 0 w a s s e l e c t e d t o t e s t t h e C T A - m a s t c e l l h y p o t h e s i s . T h i sd o s a g e s t i ll p r o d u c e d s i g n i f ic a n t t a s t e a v e r s i o n , b u t w i t h o u tt h e m o r b i d i t y a s s o c i a t e d w i t h t h e 2 m g / k g d o s a g e . I n o r d e r t ot e s t t h e p o s s i b l e p r o p h y l a c t i c e f f e c ts o f c h l o r p h i n e r a m i n et o w a r d c o n d i t i o n e d s u c r o s e t a s t e a v e r s i o n , t h i s s u b s t a n c ew a s i n i t ia l l y i n j e c t e d i n t o 6 0 - 7 0 d a y o l d m a l e W i s t a r r a t s o n eh r before s u c r o s e a v a i l a b i l it y o n t h e c o n d i t i o n i n g d a y . H o w -e v e r , w e f o u n d t h a t t h e 1 2 r a t s t h a t h a d b e e n i n j e c t e d w i t ht h e a n t i h i s t a m i n e ( 2 0 m g / k g ) v o l u m e s c o n s u m e d o n l y

1 1. 3 _+ 4 . 9 m l o f s u c r o s e c o m p a r e d t o t h e s a l i n e - i n j e c t e dc o n t r o l s , 2 2 . 9 _+ 3 . 8 m l . S i n c e t h e d i f f e r e n t i a l c o n s u m p t i o no f th e C S w a s a c l e a r c o n f o u n d i n g v a r i a b l e [ 2 ,3 ] , t h i s e x p e r -i m e n t w a s t e r m i n a t e d . W e d e c i d e d t o i n je c t t h e a n t i h is t a m i n ea f t e r th e i n i ti a l s u c r o s e c o n s u m p t i o n b u t b e f o r e t h e L i C I , C4 8 /8 0 o r s a l i n e p a i r i n g s .METHOD

E x p e r i m e n t a l l y n a i v e 7 0 - 8 0 d a y o l d ( 3 2 0 _ 2 5 g ) m a l eW i s t a r r a t s w e r e e x p o s e d t o th e p a r a d i g m u n t i l t h e c o n d i t i o n -i n g d a y . W i t h i n 3 0 m i n a f t e r t e r m i n a t i o n o f s u c r o s e a v a i l a b i l -i t y , 1 2 r a ts w e r e i n j e c t e d I P w i t h 2 0 m g / k g ( 2 c c / k g ) o f c h l o r -p h e n i r a m i n e m a l e a t e [ 8] w h i l e a n o t h e r 1 2 r a t s w e r e i n j e c t e dw i t h p h y s i o l o g i c a l s a l in e ( 2 c c / k g ) . O n e h r l a t e r , e q u a l n u m -b e r s o f r at s f ro m e a c h o f th e t w o p r e t r e a t m e n t g r o u p s w e r ei n j e c t e d I P w i t h e i t h e r L i C I ( 10 c c / k g ) , 1 m g / k g C 4 8 /8 0 ( 2c c / k g ) o r p h y s i o l o g i c a l s a l i n e (2 c c / k g ). F o l l o w i n g th e t y p i c a lt w o d a y r e c o v e r y p e r i o d , s u c r o s e s o l u t i o n s w e r e a g a i n p re -s e n t e d o n t h e t e s t d a y .RESULTS

T h e m e a n s a n d s t a n d a r d d e v i a t i o n s f o r g r o u p s u c r o s ep r e f e r e n c e s c o r e s a r e p r e s e n t e d i n T a b l e 1 . A t w o - w a yA N O V A d e m o n s t r a t e d a s i g n if ic a n t p r e t r e a t m e n t d i f fe r e n c e ,F ( 1 , 1 8 ) = 5 . 7 2 , p < 0 . 0 5 ; t h e a n ti h is ta m i n e a p p e a re d toe n h a n c e t h e C T A . H o w e v e r , t h e r e w e r e n e i t h e r si g n if i ca n tt r e a t m e n t ( L i C l , C 4 8 /8 0 o r s a l i n e ) , F ( 2 , 1 8 ) = 2 . 2 4 , n s , n o rt r e a t m e n t b y p r e t r e a t m e n t i n t e r a c t i o n s , F ( 2 , 1 8 )= 2 . 5 4 , n s .E X P E R I M E N T 4

C h l o r p h e n i r a m i n e a t d o s a g e s s u f f ic i e n t t o b l o c k C T A t os a c c h a r i n w h e n i n j e c t e d b e f o r e p r e s e n t a t i o n o f i o n i z in gr a d i a t io n d i d n o t p r e v e n t C T A w h e n s u c r o s e w a s p a i r e d w i t he i t h e r L i C I ( a re p l i c a t i o n o f [ 8]) o r C 4 8 / 80 . H o w e v e r , i n t h eL e v y [ 8] s t u d y , o n l y a s i n g le i n j e c t io n ( t h e a n t i h i s t a m i n e )w a s i n v o l v e d ( s i n c e t h e U C S w a s h a r d c o r e r a d i a t i o n ) w h i l ei n E x p e r i m e n t 3 , t h e t w o s e p a r a t e i n j e c t io n s o f p r e t r e a t m e n ta n d t r e a t m e n t a p p e a r e d t o a t t e n u a t e t h e C T A f o r b o th L i C Ia n d C 4 8 /8 0 ra t s c o m p a r e d t o t h e r e s u l t s o f E x p e r i m e n t s 1a n d 2 . S i n c e a p e r i o d o f a b o u t 1 h r e l a p s e d b e t w e e n t h e t w oi n j e c ti o n s fo r e a c h r a t , t h e p o s s i b i l i ty o f s o m e c o m p o u n d i n ga n t a g o n i z in g e f f e c t f ro m t h is p r o c e d u r e e x i s t e d . S i m i l a r o b -s e r v a t i o n s w e r e m a d e b y D o m j a n a n d B e s t [ 5]. C o n s e q u e n t -

T a b l e 1MEANS AND STANDARD DEVIATIONS ( _+ ) OF SUCROSE PREFEREN CE SCORESFOR RATS TH AT W ERE PRETREATED WITH EITHER CHLORPHENIRAMINE (20MG/KG), OR PHYSIOLOGICALSALINE AND THEN TREATED 1 HR LA TER WITHEITHE R 0.15M LICL (10 CC/KG), COMPOUND 48/80 (1 M G/KG) OR PH YSIOLOGICALSAL INE (2 CC/KG) IN EXPERIMENT 3

Treatment CombinedP r e t re a t m e n t S a l in e L i C l C 4 8 / 8 0 P r e t re a t m e n t(n= 12/group)Salin e 1.06 _ 0.08 b 0.84 __ 0.06 0.72 +- 0.08 0.87 _+ 0.16 aAn tihist am ine 0.69 -+ 0.20 a 0.75 _+ 0.22 0.69 -+ 0.23 0.71 -+ 0.20 bC o m b i n e dTre atm en t 0.88 +- 0.24 0.80 -+ 0.15 0.70 -+ 0.16(n=8/group)

a v s b p < 0 . 0 5 .


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728 PERS INGE R AND FISS

TABLE 2MEANS AND STANDARD DEVIATIONS ( _+ ) OF SUCROSE PREFERENCE SCORESFOR RATS THAT WERE PRETREATED WITH EITHER CHLORPHENIRAMINE (20MG/KG) OR PHYSIOLOGICAL SALINE AND THEN TREATED WITHIN 30 SEC WITHEITHER 0.15M LICL (10 CC/KG), COMPOUND 48/80 (1 MG/KG) OR PHYSIOLGICALSALINE (2 CC/KG) IN EXPERIMENT4

Treatment CombinedPretreatment Saline LiCI C 48/ 80 Pretreatment(n-24/group)Saline 0.88 _+ 0.26 0.72 _+ 0.14 1.00 _+ 0.30 0.87 _+ 0.26~Antihistamine 0.76 -+ 0.13 0.57 _+ 0.19 0.61 -+ 0.16 0.65 _+ 0.18hCombinedTreatment 0.82 _+ 0.21~ 0.64 _ 0.18h 0.81 _+ 0.31(n = 16/group)

a vs b p


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M A S T C E L L S A N D T A S T E A V E R S I O N 7 2 9

'b

4

A B

Li! ~

C

.... .... /!i ~,~

b

D E FF I G . 3 . P h o t o m i c r o g r a p h s o f r e p r e s e n t a t i v e m a s t c e l l s f r o m m e s e n t e r i e s o f r a t s th a t h ad b e e n e i t h e r p r e tr e a t e d w i t h p h y s i o l o g i c a l s a l in e a n dt r e a t e d w i t h s a l i n e ( A ) , L i C I ( B ) o r c o m p o u n d 4 8 /8 0 ( C ) o r p r e t r e a t e d w i t h a n t i h i s t a m i n e an d t h e n t r e a t ed w i t h s a l i n e ( D ) , L iC 1 ( E ) o r

C o m p o u n d 4 8 /8 0 ( F ) . 4 0 0 m a g n i f i c a t i o n ; t o l u i d i n e b l u e 0.

T A B L E 3M E A N S A N D S T A N D A R D D E V I A T I O N S O F H I S TO L O G IC A L S C O R E SF O R T H E D E G R E E O F M E S E N T E RI C M A S T C E L L D E G R A N U L A -T I O N F R O M 3 6 R A T S T H A T H A D B E E N P R E T R E A T E D W I T H E I T H E RC H L O R P I- IE N I R A M IN E ( 2 0 M G / K G ) O R P H Y S I O L O G I C A L S A L I N EA N D T H E N T R E A T E D W I T H E I T H E R L I C L ( 1 0 C C /K G ), C O M P O U N D4 8 /8 0 ( 1 M G / K G ) O R S A L I N E ( 2 C C /K G ) , ( N = 6 / G R O U P )

T r e a t m e n tP r e t r e a t m e n t S a l i n e L i C ! C 4 8 /8 0

S a l i n e 1 . 5 0 . 5 1 . 4 _+ 0 . 4 5 . 2 0 . 8A n t i h i s t a m i n e 1 . 4 - 0 . 2 1 . 6 - 0 . 4 5 . 5 -+ 0 . 7T o t a l 1 . 4 _ 0 . 3 a 1 . 5 - 0 . 4 a 5 . 3 0 . 7 c

a v s c p < 0 . 0 0 1 .


6/6

730 P E R S I N G E R A N D F I S S

g r o s s a l t e r a t i o n , n o t a s i n gl e M C i n a n y o f t h e m e s e n t e r i e sf r o m L i C l o r s a l i ne r a t s s h o w e d t h i s e x t r e m e p r o f i le .D I S C U S S I O N

N e i t h e r t h e p h a r m a c o l o g i c a l n o r t h e h is t o l o g i c al d a t as u p p o r t e d t h e h y p o t h e s i s t h a t m e s e n t e r i c m a s t c e l l d e g r a n u -l a t i o n i s t h e p r i m a r y c y t o l o g i c a l c o r r e l a t e o f C T A - p r o d u c i n gU C S s . L i C l - in j e c te d r a ts d e m o n s t r a t e d C T A t o t h e s u c r os es o l u t i o n b u t s h o w e d n o a p p a r e n t M C d e g r a n u l a t i o n t h a t w a ss t il l e v i d e n t o n t h e t e s t ( a n d k i ll ) d a y ; t h e i n t e n s i t y o f t h eC T A w a s q u i t e v a r i a b l e . A n t i h i s t a m i n e i n j e c t i o n s b e f o r ee i t h e r s a l i n e , L i C l o r C 4 8 / 8 0 d id n o t a l t e r M C d e g r a n u l a t i o na l t h o u g h t h e y d i d i n c r e a s e t h e o v e r a l l i n t e n s i ty o f t h e C T A .

T h e a n t i h i s t a m i n e c h l o r p h e n i r a m i n e ( 2 0 m g / k g ) a d m i n i s -t e r e d 1 h r o r 30 s e c b e f o r e L i C l d id n o t a t t e n u a t e t h e C T A , ar e s u l t s i m i l a r t o L e v y e t a l . [8 ] w h o u s e d s a c c h a r i n i n s t e a d o fs u c r o s e a s t h e C S . H o w e v e r , s i n c e L i C l d i d n o t d e g r a n u l a t e

t h e M C s w h e r e a s i o n i z in g r a d ia t i o n p r e s u m a b l y d o e s [ 11 ], itw a s p o s s i b l e t h a t t h e M C h y p o t h e s i s c o u l d s t i ll b e v al i d (f o ra t l e a s t s o m e k i n d s o f C T A ) i f t h e a n t i h i s t a m i n e c o u l d p r e -v e n t d e g r a n u l a t i o n . I n th i s s t u d y , t h e s a m e d o s a g e o f c h l o r -p h e n i r a m i n e u s e d t o b lo c k C T A i n d u c e d b y i o n i z i n g r a d ia -t i o n [8 ] d i d n o t p r e v e n t t h e d e g r a n u l a t i o n o f M C s f o l l o w i n g C4 8 /8 0 in j e c t i o n . N o d o u b t a n o p t i m a l d o s a g e a r g u m e n t s ti llc o u l d b e u s e d s i n c e t h e r e l a t i o n s h i p b e t w e e n M C d e g r a n u l a -t i o n a n d a n t i h i s t a m i n e d o s a g e c a n b e n o n - l i n e a r [1 l ] .I n a d d i t i o n t o t h e f a il u r e f o r c h l o r p h i n e r a m i n e t o b l o c kL i C l - i n d u c e d C T A [ 8 ] , t h i s s t u d y a l s o r e p l i c a t e s t h e C T Aa t t e n u a t i n g e f f e c t s o f t w o U C S s p r e s e n t e d i n c l o s e te m p o r a lp r o x i m i t y [ 5] . C T A w a s s t r o n g l y d i s p l a y e d i n b o t h E x p e r i -m e n t s 1 a n d 2 w h e r e s i n g l e L i C I o r a p p r o p r i a t e C 48 / 8 0 i n -j e c t i o n s w e r e m a d e . H o w e v e r , i n E x p e r i m e n t s 3 a n d 4,w h e r e e i t h e r s a l i n e o r a n t i h i s ta m i n e w e r e i n j e c t e d 1 h r o r 3 0s e c b e f o r e th e s e U C S s , t h e C T A w a s m a r k e d l y r e d u c e d o re v e n e l i m i n a t e d .

R E F E R E N C E S

1 . Bar ker , L . M. and J . C . Sm i th . A com par i son o f t he t a s t e aver -s ions i nduced by r ad i a t i on and l i t h ium ch lo r ide i n CS- UCS andU C S - C S p a r a d i g m s . J . c o m p . p h y s i o l . P s y e h o l . 87 : 644-654,1974.2 . Bond , N . and E . D i Gius to . A mou n t o f so lu t ion d r unk i s a f ac to rin the es t ab l i shm en t o f t a s t e aver s ion . A n i t a . L e a r n . B e h a v . 3:81-84, 1975.3 . Bo nd , N . and W . Har l and . E f f ec t o f amo un t o f so lu tion d r unkon t as t e - aver s ion l ea r n ing . B u l l . P s y c h o n . S o c . 5 : 21% 220 ,1975.4 . Csaba , G . R e g u l a t i o n o f M a s t - C e l l F o r m a t i o n . B u d a p e s t :Akademia i Kiado , 1972 .5 . Domjan , M. and M. R. Bes t . Pa r adox ica l e f f ec t s o f p r ox imaluncond i t i oned s t imu lus p r eexposur e : I n t e r f e r ence wi th andcond i t i on ing o f a t a s t e aver s ion . J . e x p l P s y c h o l . A n i t a . B e h a v .P r o c . 3: 310-321, 1977.6 . G ar c i a , J . , F . R . E r v in and R. A . Koe l l i ng . Ba i t - shyness : A t es tf o r t ox i c i t y wi th N = 2 . P s y c h o n . S e i . 7: 245-246, 1967.

7 . H u m a s o n , G . A n i m a l T i s s u e T e c h n i q u e s . S a n F r a n c i s c o :F r eem an , 1972 , p . 349 .8 . L evy , C . J . , M. E . Car r o l l , J . C . Smi th and K. G . Hof e r . An-t i h i s t amines b lock r ad i a t i on - induced t a s t e aver s ions . S c i e n c e186: 1044-1045, 1974.9 . Nach man , M. and J . H . Ashe . L ear ned t a s t e aver s ions i n r a t s a sa func t ion o f dosage , conce n t r a t i on , and r ou t e o f admin i s t r a t ionof L iCI . P h y s i o l . B e h a v . 10 : 73-78, 1973.10. Pe r s inger , M . A . Mas t c e l l s i n t he b r a in : Poss ib i l i ti e s f o r phys i -o log i ca l p sycho logy . P h y s i o l . P s y c h o l . 5: 166-176, 1977.l l . S e y l e , H . T h e M a s t C e l l s . Wash ing ton : Bu t t e r swor ths , 1965 .12. Smi th , D . E . I n f luence o f an t ih i s t amin ics on ma s t ce l l d i s r up t ionf o l lowing X - i r r ad ia t i on . P r a c . S o c . e x p . B i o l . M e d . 97: 872-874,1958.13 . Smother man , W. P . , J . W. Hennessy and S . L ev ine . P l asmacor t i cos t e r one l eve l s a s an i ndex o f t he s t r eng th o f i l l ness i n -duced t a s t e aver s ions . P h y s i o l . B e h a v . 17: 903-908, 1976.

1978 - persinger & fiss - pharmacology, biochemistry & behavior - mesenteric mast cell degranulation...

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