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EFFECTS OF LEAD ADMINISTRATION ON POSTNATAL DAY 5 OR D^Y^5^»p£«p=i 

LIFE ON LITHIUM-INDUCED POLYDIPSIA, STRIATAL *H-SPMJERONE BINDING 

AND DOPAMINE METABOLISM IN ADULT RATS... R.B. HailmdnUD.-L, DeHaven 

ond M.R. Krigman- Biol. Sci. Res. Ctr. aod Depts. pitPbonuic&lljM 

Poychiot. ,ond Pathol., Univ. Horth Carolina Sch. Med!;,; ChapelWnj\)' 

'Hill, NC 27514 ••,.• • ." ' '••: •• •" '-jl'" '"'[•'••"•''•..'• ""' 

Lithiua-induced polydipsia (LIP) has been ohown tto be increased 

in adult rata who uere treated uith lead (Pb) fros aa y 3 to day~30 

of life (Mailoan et al.. Science. 201:637, 1978). ffhis jSfitec 

peroanent, is not caused by higher doses of lead adpinifftexed. 

s^oFS^'^aaa -'EVIDENCE1' THA.,,; LOM-LEVEL DEVELOPHENTAL LEAD EXPOSURE PRODUCES TOXIC 

At3LV0PIAilH0JA. Fox and A.A. Bright". Div.. o f Toxlcolooy.. Univ of 

,e'hl.. Houston, Yx lm.. . .-, • ,\ 

days 30-60 of life and is not due to differences in-^circulifting" 

renin or angiotensin or other renal changes. Lithiuo-induced 

polydipsia baa also been shown to be dependent upon an intoct niQrostriatal dopaminergic systeo, but not any other oonoaraine sys- \\ 

tea. The present enperioents have narrowed the range of ages dur-

. ing uhich Long-Evans rats are sensitive to lead-induced changes in 

LIP, and have also esaoined the function of tbe nigroatriatal dop- • 

oaine oysteo. In tbe first study, rats uere treated by oral gay-

 ; 

' age uith 200 og/hg/day of lead (as the acetate) or uith oodiua ..." 

ocetote vehicle during days 3-10, 11-20 or 21-30 of life (birth = ' 

d ay 1) . 'At 6 0 days of age, testing for LIP uas Initiated. Sig- r,..;•' 

• oif leant increases in LIP uere seen in the groups treated froa • '".. 

'. days 3-10 and 11-20, but not those treated on days 21-30. In the..'; 

, second esperioent, rato uere treated uith a single dose of lead ,. • 

. (200 og/Itg) or vehicle on either day S or day 15. A uithin-litier ;] 

, design uas used such.that each sen within a litter received one of••' 

• tbe four treotcsnts. Testing for LIP began uhen the rats uere co^ ' 

60 days of age, and the oooe rats uere sacrificed for neurocheai- •:} 

. cal analyses uhen ca. 6 Donths of oge. Individual Scatcbard anal-'; 

,, y6es of

 s H-spiperone binding uere perforaed for each rot'o striata ? 

, using unlabeled spiperone as displacer; Concentrations of dop-'"'i-'i 

• aaine, DOPAC and HVA uere quantified using HPLC uith EC detection •• 

(Kilts et ol., J. Chrooatog., 225:337, 1981). Administration:of ;'., 

'• Pb on either day S or day 15 caused a significant increase in LIP" 

compared to controls. However, uhen the onioals uere sacrificed.1 ; 

after thorough washout of lithium, there uas no difference betueen 

Pb-treated and control groups in the affinity or number of receptors for

 3 H-spiperone in the striatua. Moreover, concentrations \;'.;, 

J of DA, DOPAC and HVA in striatua uere also unchanged. These datp.'' 

. indicate the gross alterations.of nigrostriatal DA function are 

",• not observable in treated rats'uho have significant alterations of 

LIP. Houever," differences between Pb and control groups night be 

evident if these same pairaoeters were coopared while the rats, uere " 

being treated uith lithium. ; In any event, the fact that a single . 

dose of 200 ag/Bg of lead causes o change in LIP of similar oagnij tude to that induced by dosing from days 3-30 suggests that this . • •' 

effect is a sensitive oonitor of lead exposure during - development. 

(Supported in part by ES-01104, ES-02087 and HD-03110). " 

lashevoiced recoyfcrv functions suggested tliat" Pb effects jsl^ht 

Tjuiwriiatpri, Conductio Ijctlonve'lorrrre n v'^locrrf s ot the hlon IH I and 

conduction anTup orgs were decreas decreasee d \n tnp_j>b group uith 

If-ia m/s'ec ws 13-lb m/sec IPb vs t) for theft~gr5up 

and 4.2-5.6 a/tec vs 5.2-7.0 ra/sec for the H group, .throngyy 

•"?) Hfifr. toz-*b*-&ABi£ conduction groups were M -

with ranges of 68-130 ps vs 39-59 vs for the H group and 125-148 

ps vs 53-69 ws for the M group. Postsynaptic response latencies 

for the H and H conduction groups recorded form the L6N, SC, and 

CX uere also Increased bu^ increases 1n th<- r»rnm>rv response 

latencies and their amplitudes orfiy occurred In the cortica) 

jFEEgVery functions, latency increases TTTthe response components 

^T"r!t^xi^y"recor3ia 1n Pb-exposed rats appear to be the "result 

o f a decrease in the conduction velocity and excitability of the 

•'Y/ITT. .inn mrnM"" conduction ortmbs in the ON. InfPeases In latency and amplitude o f the recovery responses of the retlnogenlculate component do not occur 1n the LGN which suggests that neonatal Pb exposure affects the cortical recovery mechanism. 

Supported by grants ES 02713 and OH 07085. 

••:•' . ."•*•: 

tXJJ 

{Reports of children poisoned by Inorganic lead'(Pb) 

_-,-^ . ^^j-eversible iopalnnents i n spatial resolution properties 

of the Visual]] systea. Experimental work from our laboratory and 

that ofjbthers suggests that deficits are confined to higher ,• 

rtj»J^al_.frequ'4nc1es and preferentially occur at scotopic, i n con-

'©S^-??j photPP^c, levels of luminance. These changes have been , < 

=PSfiart?.ttOc^ccur ot oi l levels of the visual system (Fox et nl.„: 

Tox. Appl. Tox.a0:449.1977 and Neurobehav. Tox.1:101.1979; Fox and 

Sillman. Science 206:78,1979; Bushnell et al. . Science 196:333;-r,.,.' 

1977; Impelman et al. , Heuroscl. Abs.8:1n press,1982). To deter-. '. 

ralne I f the spatial resolution limit , visual acuity, of the adult 

rat's (100 days of age) visual system uas altered following low-••";: 

level neonatal Pit exposure, electrophysiological and^psychophyslcal 

studies ttere conducted at aesoplc end scotopic .levels.of .luminance. \ 

Female.neonatal.Long-Evans hooded rats oere pxnasaLtaJBUCAC-no'*'- 5 

-Pb) from oarturltlnn tn HP»n1no Tdays_ft^LLjda the ml lie of dams •"•} 

rnn^mttrtr, » 7t Ph jcetate Joiujgi)^!^^lHJdftns."^nec>er^a^ bag; i 

gSer^reversal jgrjJjaJLeyfl&d potentials (temporal treo. UTfflTHTT ; 

• aire recoroea in chronlcafly implanted awake rats and used to es-^ i 

tlraate ^uaJJjfuU y by a codification of the extrapolation tech-' .':' 

' nlque (CampbeTToiia Haffel. J. Physiol.207:635.1970). Visual .'; 

.acuit y psychometric functions were obtained utilizin g sine-wave' 

/gratings (0.1-1.3 c/deg) in a conditioned suppression paradigm. . 

.'. . Results In control and Pb-exposed rats reveal o close corres- ' 

.pondence between electrophysiological!?, and psychophysical l y de-

' termlned spatial resolution limit . The oaximal spatial resolution' 

' In control rats aas approx. 1.3 c/deg under scotopic and oesoplc 

conditions.:These acuity values are In good.agreement uit h those 

' of Birch and Jacobs (Vis. Res.l9:933.1979) and Lennle ond Perry 

( J . Physiol.315:69.1981). Pb-exposed rats exhibited a Z5-S02 

decrease"l"n visual acuity "wtxtt greater oencit s being observed 

'WceipteiftoirnrrTOian roesopic, conditions, uecreasesm spatial res-

•=o?uLiun utrre-tmityVSd at al l Willi ' nreqmriiples greater than 0.25 

c/deg In Pb-exposed rats. In addltigp to. the.'''"'ro»epH p?p? jwpii . 

tudesf whUh account for the decrements in spatial resolution. Increases in~P2~jrmr~wrjratencies were observed in ihe Pb group. , 

[ ' inese data provide evidence that IOH-ievei neonatal >b exposure 

. produces toxic amblyopia. They also extend the findings that the 

scotopic system is core vulnerable to the toxic actions of Pb than 

the mesopic/photoplc system and provide further support for the 

; idea that al l levels of the visual system are affected by develop-

" dental Pb exposure. 'Further experiments to determine the specific 

. s1te(s) and mechanlsm(s) of action are In progress: Supported by 

grants ES 02713 and OH 07085. 

CVS 

3 CENTRAL EFFECTS OF L(W LEVEL DEVELOPHENTAL LEAD EXPOSURE ON OPTIC 

NERVE CONDUCTION AND THE RECOVERABILITY OF GENICUL0C0RTICAL • . 

,.;RESPONSES IK HOODED,RATS. P. Impeloan". C.L. Leara. R. mison^i v 

v ond D.A. Fox (Spon. B. Brooks). Div. of Tox. Univ. Texas Hed. * '• 

Schl,. Houston, TX 77025. 

Long-term effects on visual functions 1n rats , following lowlevel neonatal lead (Pb) exposure suggest that clinical reports 

of Irreversible Impairments In spatial and temporal resolution 

properties of the visual system 1n children are partly due to 

changes in bioelectric properties of the optic nerve (ON) and in 

recoverablllty of visual cortical responses. Following neonatal 

. Pb exposure latencies of the retinogeniculate and retlnocolllcular 

responses of flash visual evoked cortical, potential (VECP) In 

adult rats are Increased (Fox et al. , Tox. Appl. Pharm. 40:449, 

1977 and Neurobehav. Tox. 1:101, 1979). Latency increases In 

these pathways saay reflect a decrease in the conduction velocity 

.and excitabilit y of the ON fibers since postnatal exposure to Pb 

: produces hypoqyellnatlon and a decrease in fiber diameters of the 

ON (Tennekoon et al. , Ann. Neurol. 5:558, 1979). ^.Conduction veJoc1t1eS-JUldJJlcQnaxy vaTues obtained for the three UN conduction' 

groups'and the postsynaptic response latencies were measured in 

electrically evoked potential recordings from the LG>L_5HnerlPr 

- CQl'llcufuTTSCTr and the striate corTeJTTtX_L1n aduftcactrql and 

Vp"iV'eated iong-tvans hooded rats remaie rats were exposed to 

^TD lOV'no v.) from parturition tp'weaning (days 0-21) via the 

milk of dams consuming 0.22 Pb acetate solutions (or water).JGectrica l jatoted rgcoverv responses to doiMe-Julsje-jAlmHlaJdMLftf,, 

'lipnliw w rpcorded because the similarity of electrical and 

23/1 ElffiVKWAL DEFICITS IM KCNKEYS EXPOSED TO ICW LEVUS CF LITiD 

SIKCE BIRTH. Deborah C. Rice 'and Steven G. Gilbert" (Spon: 

rtijrj-i.. • '•• jf B. Heiso ).' Itucioology Rsssarch Division, Bureau"oT Otgnical" 

, • Safety, Food Directorate, Haalth Protection Branch, Health and 

Welfare Canada, Tunney's Pasture, Ottawa, Ontario, Canada KIA 0L2. 

tonkeys (Macaca fascicularis) uere dosed orally from birth with 

0, 50, or 100 ugAg/day of lead es lead ecetate. Blood lead 

levels peaked at 16 or 22 ug/dl by 100 days of age for the two 

treated groups respectively, and decreased after Meaning at 200 

daysC'of ege to 12 ug/dl in both groups. Blood lead levels for 

oontrol monkeys vere always bslow the level of detection of ^he 

analytical procedure (5 ug/dl). (Bien the nonkeys uere approximately three years old, they vers tested on a tKO-choice discrimination and series of reversals paradigm. Die monkeys faced a 

panel on uhich uere a tube for delivery of fruit juice and two 

' clear plastic response disks that could be backlit with various 

stimuli. Ots stimulus display consisted of a tup-dimensional 

form (square or triangle) and color (red or green) on each disk. 

During the first part of the experiment, both disks uere always 

backlit uith red, and the BDnkey uas required to respond on the 

disk displaying the square in order to receive a email onount 

of apple juice. The disk on which the correct stimulus appeared 

uas varied randomly from trial to trial. Hhen the monkey had 

learned ths task (at least 9 out of 10 correct in a 10-trial 

block), the correct stimulus became tlie previously incorrect one, 

and the nankey had to releam the task. A total of 20 such 

reversals uere performed. Fbr the tuo following tasks, ths form 

and colors were displayed independently of each other, uith one 

disk displaying one color and form, and the other disk the other 

possible pair. For tte second task the monkey was required to 

attend to the colors cn ths disk and ignore ths forms (initially 

red correct), while far the third task the forms uere the relevant stimuli and ths colors irrelevant (initially triangle 

correct). Twenty reversals were performed cn each task. For 

each task, there were monkeys in the two treated groups whose 

performances uere outside of control range on the reversal eerie%, 

taking langer to learn the reversals and making more total 

errors than controls. 

S