Saccharin-Induced Increase in Daily Fluid Intake

8/12/2019 Saccharin-Induced Increase in Daily Fluid Intake

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Pergamon

0031-9384 94)00389-0

Ph y s i o l o g y & B e h a v i o r, Vo l . 5 7 , No . 4 , p p . 7 9 1 -7 9 5 , 1 9 9 5C o p y r i g h t 1 9 9 5 E l se v i e r Sc i e n c e L t dPr i n t e d i n t h e USA . Al l r i g h t s r e se rv e d

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as a P red i c to r o f Vo lu n t a ry Alco h o l In t ak e i nA l c o h o l P r e f e r r i n g R a t s

A L E X E Y B . K A M P O V - P O L E V O Y, ~ D AV I D H . O V E R S T R E E T , A M I R H . R E Z VA N IA N D D AV I D S . J A N O W S K Y

S k i p p e r B o w l e s C e n t e r f o r A l c o h o l S t ud i e s , M e d i c a l R e s e a r c h B l d g . A , C B 7 1 7 5, U n i v e r s i ty o f N o r t h C a r o l i n a C h a p e l H i l l S c h o o l o f M e d i c i n e , C h a p e l H i l l, N C 2 7 5 9 9 - 7 1 7 5

R e c e i v e d 21 M a r c h 1 9 94

K A M P O V- P O L E V O Y , A . B ., D . H. O V E R S T R E E T, A . H . R E Z VA N I A N D D . S . J A N O W S K Y.Saccharin-induced increasein da ily luid intake as a pre dictor of voluntary alcohol intake in alcohol-preferrring rats.PHYSIOL B EHAV 57(4 ) 791-795 ,19 95 .--T his study exam ined the relationship betw een saccharin intake and ethanol consum ption in alcohol preferring (P) rats andFawn Hooded (FH) rats before and after exposure to forced ethanol (10%, v/v) solution. Both groups exhibited large increases(> 2X ) in daily fluid intake (DFI) when saccharin (0.1%, w/v ) was present and exhibited moderate leve ls of ethanol intake. Onlythe P rats significantly increased their ethanol consumption after exposure to ethan ol as the sole drinking fluid. Correlationalanalyses revea led that the absolute intakes of saccharin and ethanol w ere not significantly correlated in either group, but theincrease in D FI in the presenc e of saccharin was high ly correlated with ethanol intake after forced ethanol exposure (r > +0.8 ; p< 0.05). Sim ilarly, when correlatio ns were conducted for these variables o ver both the P and FH groups, the correlation betweenincrease in DFI in the presence of saccharin and alcoho l intake was significantly higher than that betwee n saccharin and alcoh olintakes. R eexam ination of previous data from 6 different rat s trains also revea led a significant correlation betw een increase in DFIin the presence of saccharin and ethanol intake. These findings suggest that the dramatic increase in of DFI in the presence ofsaccharin ma y be an anim al analog of the clinical phenom enon kn own as a loss of control.

Saccharin intake Alc ohol intake Loss of control Alco hol preferring P rats Faw n-H ooded rats

A P O S I T I V E a s s o c i a ti o n b e t w e e n t h e c o n s u m p t i o n o f t h e p a l -a t a b l e s o l u t i o n s a n d a l c o h o l i n t a k e h a s b e e n d e m o n s t r a t e d i n an u m b e r o f a n i m a l s t u di e s. F o r e x a m p l e , C 5 7 B L m i c e , w i t h ag e n e t i c p r e d i s p o s i t i o n t o d r i n k a l c o h o l , a l s o c o n s u m e d l a rg e ra m o u n t s o f a h i g h l y p a l a t a b l e s a c c h a r i n s o l u t i o n t h a n D B A m i c e ,w i t h a g e n e t i c p r e d i s p o s i t i o n t o a v o i d a l c o h o l ( 6 , 2 8 ) . S i m i l a r r e -s u i ts w e r e f o u n d i n p o p u l a t i o n o f Wi s t a r ( 1 5 ) a n d r a n d o m l y b r e dr a t s ( 7 ) . A n e v e n s t r o n g e r a s s o c i a t i o n b e t w e e n s a c c h a r i n a n d a l -c o h o l i n t a k e s w a s d e m o n s t r a t e d i n ra t s tr a i n s ( A A & A N A , P &N P, F H ) w i t h d i f f e r e n t p r o p e n s i t i e s t o d r i n k a l c o h o l( 1 2 , 1 4 , 2 6 , 3 1 ) . T h e m o s t r e c e n t s t u d y, w h i c h e x a m i n e d s a c c h a r i na n d e t h a n o l c o n s u m p t i o n i n 1 5 in b r e d m o u s e t r a in s , c o n f i r m e dt h e h i g h p o s i t i v e a s s o c i a t i o n ( r = + 0 . 7 7 ) b e t w e e n t h e s e t w o v a r i -a b l e s ( 4 ) a c r o s s s t r a in s a n d s u g g e s t e d t h a t g e n e t i c f a c t o r s l a rg e l ya c c o u n t e d f o r t h is c o r r e l a t i o n .

O u r r e c e n t s t u d i e s s h o w e d t h a t i n a d d i t i o n t o a n a s s o c i a t i o nb e t w e e n s a c c h a r i n a n d a l c o h o l i n t a k e, a l c o h o l - p r e f e r r i n g r a t s d ra -m a t i c a l l y i n c r e a s e d t h e i r d a i l y f l u id i n ta k e ( D F I ) w h e n s a c c h a r i ns o l u t i o n w a s o f f e r e d a l o n g w i t h w a t e r . T h i s p h e n o m e n o n w a s

f i rs t d e m o n s t r a t e d i n a p o p u l a t i o n o f r a n d o m l y b r e d r a t s ( 1 5 ) a n dt h e n i n N I H H e t e r o g e n e o u s s t o c k ( H S ) r a t s ( 1 3 ) . I t w a s a l s of o u n d t h a t a l c o h o l - p r e f e r r i n g P a n d F H r a ts a l m o s t t r i p l e d t h e i ru s u a l D F I w h e n s a c c h a r i n s o l u t i o n w a s a v a i l a b l e ( 14 , 2 6 ). O n t h eo t h e r h a n d , t h o s e r a t s w i t h a l o w i n t a k e s o f a l c o h o l u s u a l l y d r a n ks a c c h a r i n s o l u t i o n w i t h i n t h e l i m i t s o f t h e i r D F I , a l t h o u g h t h e i rp r e f e r e n c e f o r s a c c h a r i n w a s a s h i g h a s t h o s e r a t s w i t h h i g h a l -c o h o l i n t a k e s ( 1 4 , 2 6 ,3 1 ) . S u c h a n i n c r e a s e o f D F I i n a n i m a l se x p o s e d t o s a c c h a r i n so l u t i o n m a y b e a n a n i m a l m o d e l o f t h ec l i n ic a l p h e n o m e n o n k n o w n a s l o s s o f c o n t r o l . L o s s o f c o n -t r ol , w h e n t h e s u b s t a n c e o f t e n i s ta k e n i n l a rg e r a m o u n t s o r o v e ra l o n g e r p e r i o d t h a n t h e p e r s o n i n t e n d e d , i s a c o m m o n p h e n o m -e n o n w i t h i n t h e e a t i n g d i s o r d e r s a n d s u b s t a n c e a b u s e r e g a r d l e s so f t h e d r u g o f c h o i c e ( 2 , 1 0 ) . Ta k i n g i n t o c o n s i d e r a t i o n t h e h i g hl e v e l o f c o m o r b i d i t y ( u p t o 6 0 % ) b e t w e e n e a t i n g d i s o r d e r s a n ds u b s t a n c e a b u s e ( 1 0 ) a n d t h e f a c t th a t e l e m e n t s o f e a ti n g d i s o r -d e r s c a n b e d e t e c t e d l o n g b e f o r e t h e d e v e l o p m e n t o f a l c o h o la b u s e ( 11 ) , w e h y p o t h e s i z e t h a t t h e l o s s o f c o n t r o l o v e r t h e s a c -c h a r i n i n t a k e m a y r e f l e c t a p r o p e n s i t y t o t h e d e v e l o p m e n t o f a n

Portions of this paper wer e presented at meeting s of Research Society of Alcoh olism, San Anton io, Texas, June 19-24, 1993, 2nd InternaBehav ioral Neuros cience Socie ty Conf erence, April 22-25, 1993, Clearwater, Florida.

To w hom req uests for reprints should be addressed.

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792 KAMPOV- POLEVO Y ET AL.

TABLEPARAMETERS OF INITIAL DAILY FLUID INTAKE (DFI) AS WELL AS DFI IN PRESENCE OF SACCHARIN BEFORE

AND AFTER INITIATION PROCEDURE (EXPOSURE TO 10 ALCOHOL SOLUTION AS A SOLE SOURCE OFFLUIDS FOR 5 DAYS) IN P AND FH RATS (M _+ SEM).

P Rats FH Rats F p

Initial DFI (ml/kg/day) 75.3 3.2 145.1 13.1 29.671 8 0 ) by all rats, regardless of propensity to drinkalcohol.

Positions of bottles were rotated daily to prevent place pref-erence. Fluid intake from each bottle was measured each day andcorrected for the body weights of the rats. The increase in DFIin the presence of saccharin was calculated as a percent differ-ence betwe en total fluid intake when saccharin was availa ble andthe total fluid intake when only water was available.

Statistical nalyses

Comparisons of alcohol and saccharin intake between lineswere computed with the analysis of variance with Fisher LSDposthoc comparisons. Pearsonian correlations between the vari-ous measures of saccharin consumption (intake, preference andincrease in DFI) and a lcohol intake were also performed.


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7 94 K A M P O V - P O L E V O Y E T A L.

i n a s u b s t a n t i a l i n c r e a s e i n t h e i r D F I w h e n s a c c h a r i n w a s p r e s -e n t ( Ta b l e 1 ). T h i s i n c r e a s e i s a l m o s t 1 0 t i m e s h i g h e r t h a n t h a tr e p o r t e d f o r W i s t a r r a t s ( 1 5 ) a n d , u n l i k e W i s t a r r a t s , t h e i n -c r e a s e i n D F I w a s d e m o n s t r a t e d b y a l l F H a n d P ra t s. T h i si n c r e a s e i n D F I w a s a l s o s h o w n t o b e t h e m o s t r e l i a b l e p r e -d i c t o r o f s u b s e q u e n t a l c o h o l c o n s u m p t i o n i n P a nd F H r a t s( Ta b l e 3 ) , a s it w a s m o s t c o n s i s t e n t l y c o r r e l a t e d w i t h a l c o h o li n t a k e a n d w a s s i g n i f i c a n t l y m o r e h i g h l y c o r r e l a t e d t h a n s a c -c h a r i n i n t a k e o n o n e o c c a s i o n . T h e r e a s o n f o r t h i s o u t c o m em a y b e r e l a t e d t o t h e f a c t t h a t t h e i n c r e a s e i n D F I i s t h e v a r i -a b l e t h a t i s l e a s t d e p e n d e n t u p o n t h e b a s e l i n e D F I , w h i c h d i f -f e r e d s u b s t a n t i a l l y i n t h e P a n d F H r a t s ( Ta b l e 1 ).

A l c o h o l i n t a k e s f o r t h e P a n d F H r a ts a r e m o d e s t ( Ta b l e 2 )a n d s u b s t a n t i a l l y l o w e r th a n v a l u e s w h i c h h a v e b e e n r e p o r t e di n t h e l i t e r a t u r e ( 1 6 ,2 4 ) . I n p a r t , t h e s e l o w e r v a l u e s m a y b er e l a t e d t o th e s h o r t d u r a t i o n o f e x p o s u r e o f t h e a n i m a l s t oe t h a n o l ( 1 0 d a y s b e f o r e a n d a f t e r f o r c e d e x p o s u r e ) , s i n c e i t i st y p i c a l t o e x p o s e t h e r a ts t o a t l e a st 2 1 d a y s o f c h o i c e c o n d i -t i o n s a f t e r t h e e x p o s u r e t o f o r c e d a l c o h o l ( 1 , 1 9 , 2 7 ,3 3 ) . I t i sa l s o p o s s i b l e t h a t t h e r e d u c e d a l c o h o l i n t a k e m a y b e c o n s e -q u e n c e o f t h e p r i o r e x p o s u r e t o s a c c h a r i n ( 1 6 , 1 7 ) . I n a n y c a s e ,t h e i n c r e a s e i n a l c o h o l i n t a k e i n t h e P r a t s , b u t n o t t h e F H r a t s ,

a f t e r f o r c e d e x p o s u r e t o a l c o h o l ( Ta b l e 2 ) r e p l i c a t e s o u r p re -v i o u s l y p u b l i s h e d w o r k ( 2 6 ) .

T h e f a c t t h a t i n c r e a s e i n D F I i n t h e p r e s e n c e o f s a c c h a r i n w a st h e b e s t p r e d i c t o r o f a l c o h o l i n t a k e i n t h e p r e s e n t s t u d y l e d u s t or e e x a m i n e d a t a f r o m a p r e v i o u s s t u d y ( 2 6 ). W h e n c o r r e l a t i o n sb e t w e e n i n c r e a s e i n D F I a n d a l c o h o l i n t a k e w e r e c a r r i e d o u t f o rp a i r s o f a l c o h o l p r e f e r r i n g a n d n o n p r e f e r r i n g r a t s t r a i n s / li n e s , s i g -n i f i c a n t p o s i t i v e a s s o c i a t i o n s w e r e f o u n d f o r a l l p a i r s ( N P & P ;M R & M N R A ; F H & F R L ) . T h e s e c o r r e l a t i o n s w e r e a t l e a s t a ss t r o n g a s t h o s e f o r sa c c h a r i n i n t a k e a n d a l c o h o l i n t a k e ( r > 0 . 6 ;P < 0 . 0 5 ). H o w e v e r, t h e s a c c h a r i n i n t a k e c a n g i v e m i s l e a d i n gp i c t u r e f o r i n t e r s t r a in c o m p a r i s o n s , m o s t l y b e c a u s e o f t h e d e -p e n d e n c y o f t hi s m e a s u r e o n t h e b a s el i n e D F I , w h i c h v a r i es f r o ms t ra in to s t ra in . No te tha t i n Ta b le 1 , t he P ra t s ha ve s ign i f i c a n t ly

l o w e r b a s e l i n e D F I a n d s a c c h a r i n i n t a k e t h a n t h e F H r a ts , b u tt h e i r s c o r e s f o r i n c r e a s e i n D F I a r e s i m i l a r. O v e r a l l , t h e p r e s e n tf i n d i n g s i n d i c a t e t h a t a lt h o u g h s a c c h a r i n i n t a k e m a y i t s e l f c o r -r e l a t e w i t h s u b s e q u e n t a l c o h o l i n t a k e u n d e r s o m e c i r c u m s t a n c e s ,

a s r e p o r t e d p r e v i o u s l y ( 4 , 2 6, 3 1 ) , t h e i n c r e a s e i n D F I i n t h e p r e s -e n c e o f s a c c h a r i n i s a m o r e r e l i a b l e p r e d i c t o r o f s u b s e q u e n t a l -c o h o l i n t a k e ( Ta b l e 3 ) .

T h e d r a m a t i c i n c r e a s e i n D F I i n t h e p r e s e n c e o f s a c c h a r i ne x h i b i t e d b y t h e F H a n d P r a t s m a y b e a n a n i m a l a n a l o g o f t h ec l i n ic a l p h e n o m e n o n k n o w n a s " l o s s o f c o n t r o l . " T h i s p h e n o m -e n o n r e f e r s to s i t u a t io n w h e r e f o o d o r t h e d r u g o f c h o i c e i s ta k e ni n l a rg e r a m o u n t s o r o v e r a l o n g e r p e r i o d s o f t i m e t h a n t h e p e r s o ni n t e n d e d . I t h a s b e e n d e s c r i b e d f o r e a t i n g d i s o r d e r s a s w e l l a s f o rt h e s u b s t a n c e a b u s e ( 1 0 ) a n d m a y r e f l e c t s o m e b a s i c i n a b i l i t y t oc o n t r o l t h e p l e a s u r a b l e s t i m u l i . I n t h is s t u d y, t h e l o s s o f c o n t r o lm a y b e e a s i l y s e e n w h e n s a c c h a r i n i s a v a i l a b l e ; t h e a n i m a l s a l -m o s t t r i p l e t h e i r D F I . H o w e v e r, i t i s n o t s o o b v i o u s f o r a l c o h o li n t a k e , a s t h e i r v a l u e s w e r e l o w e r t h a n h a s b e e n t y p i c a l l y r e p o r t e di n t h e l i te r a t u r e. T h e p o s s i b l e r e a s o n s f o r t h is l o w a l c o h o l i n t a k ei n th e f a c e o f " o u t o f c o n t r o l " d r i n k in g o f s a c c h a r in h a v e b e e nd i s c u s s e d b r i e f l y a b o v e . O n e o t h e r f a c t o r t o c o n s i d e r h e r e i s t h a tu n l i k e t h e p r e f e r e n c e f o r s w e e t t a s te s t h a t a p p e a r s t o b e u n l e a r n e da nd oc c u rs a s e a r ly a s s e ve ra l hours a f t e r b i r th (Se e 18 ) , t hep r e f e r e n c e f o r a l c o h o l i n a n i m a l s n e e d s t o b e d e v e l o p e d a n d , i nm a j o r i t y o f c a s e s , t o b e e n h a n c e d b y s p e c i a l p r o c e d u r e s , s u c h a sp r o l o n g e d a n d / o r f o r c e d e x p o s u r e t o e t h a n o l ( 1 , 1 6 ,2 7 , 3 3 ) o r f a d -

i n g p r o c e d u r e ( 2 9 ) .O n e p o t e n t i a l n e u r o c h e m i c a l m e d i a t o r o f t h i s a s s o c i a t i o n b e -

t w e e n i n c r e a s e i n D F I i n t h e p r e s e n c e o f s a c c h a r i n a n d a l c o h o li n t a k e c o u l d b e s e r o t o n i n . I t h as b e e n h y p o t h e s i z e d t h a t t h e s e r o -t o n e rg i c s y s t e m m o d u l a t e s a p p e t i t i v e b e h a v i o r r e g a r d l e s s o f t y p eo f r e i n f o r c e r ( f o o d , a l c o h o l ) b y f a c i l i t a t i n g c e s s a t i o n / s a t i e t ym e c h a n i s m s , r a th e r t ha n b y s u p p r e s si o n o f c r a v i n g ( 2 3 - 2 5 ) . T h ef a c t t h a t b o th F H a n d P r a ts , w h i c h a r e k n o w n f o r d y s f u n c t i o no f b ra i n s e r o t o n e rg i c s y s t e m s ( 3 , 5 ,8 , 9 , 2 1 ,3 0 , 3 5 ) d e m o n s t r a t e t h el a c k o f c o n t r o l o v e r s a c c h a r i n i n t a k e a n d a l s o c o n s u m e l a rg ea m o u n t s o f a l c o h o l i s c o n s i s t e n t w i t h t h i s h y p o t h e s i s . F u r t h e rs u p p o r t c o m e s f r o m s t u d i e s d e m o n s t r a t i n g t h a t t h e i n t a k e s o fb o t h a l c o h o l a n d s w e e t p a l a t a b l e s o l u t i o n s c a n b e m o d i f i e d b yd r u g s i n t e r a c t i n g w i t h t h e s e r o t o n e rg i c s y s t e m ( 2 2 , 2 7 , 3 0 ) .

ACKNOWLEDGEMENTS

The authors thank Dr. T.-K. Li and Indiana A lcoho l Research Cente r(P50-AA07611) for providing the P rats .

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