Alcohol 26 (2002) 155–161

0741-8329/02/$ – see front matter © 2002 Elsevier Science Inc. All rights reserved.PII:

S0741-8329(02)00194-5

Ethanol self-administration in Maudsley reactive and Maudsley nonreactive inbred rats

Nelson Adams

a,

*, Pamela S. Mitchell

a

, Santiba D. Campbell

a

, Herman H. Samson

b

a

Department of Social Sciences, Winston-Salem State University, 601 Martin Luther King, Jr. Drive, Winston-Salem, NC 27110, USA

b

Department of Physiology and Pharmacology at Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA

Received 30 July 2001; received in revised form 5 November 2001; accepted 7 December 2001

Abstract

This study was performed to investigate ethanol self-administration in inbred Maudsley rats, which were selected for differences instress susceptibility and which often differ in their home cage ethanol consumption. Adult, male, Maudsley reactive (MR/Har) and Maud-sley nonreactive (MNRA/Har) rats were tested in a standard protocol for the sucrose-substitution procedure for the initiation of self-administration of ethanol in an operant setting. Before and after initiation for self-administration in the operant setting, rats were testedfor home cage consumption of 10% (vol./vol.) ethanol in a two-bottle test for 14 consecutive days. During the sucrose-substitution proce-dure, MNRA/Har rats consumed more sucrose and ethanol than did MR/Har rats. In addition, MNRA/Har rats self-administered agreater amount of ethanol during a concentration manipulation with the use of a fixed ratio (FR) 4 response requirement. However, bothstrains self-administered low amounts of 10% ethanol (MNRA/Har, 0.15 g/kg/day; MR/Har, 0.08 g/kg/day) after concentration manipula-tion compared with those observed in outbred rats and alcohol-preferring rats tested under identical conditions in other studies. BothMR/Har and MNRA/Har rats markedly increased their ethanol intake in the home cage after the initiation protocol, but there was no dif-ference between MR/Har and MNRA/Har on that measure. The failure of MR/Har rats to self-administer ethanol was inconsistent withtheir home cage drinking in other studies, and this is distinctly different from the self-administration pattern of high-alcohol-drinking ratlines tested in this paradigm. © 2002 Elsevier Science Inc. All rights reserved.

Keywords:

Maudsley inbred rats; Operant ethanol self-administration; Sucrose substitution; Initiation

1. Introduction

The Maudsley reactive (MR) inbred rat strain, which wasoriginally selected for stress susceptibility (Broadhurst,1960), has been proposed as an animal model for excessiveethanol preference (Adams et al., 2001). Although their se-lection criterion was not ethanol related, high levels of etha-nol consumption have been reported in MR rats from theoriginal British stocks (Drewek & Broadhurst, 1979), fromthe stocks maintained at the National Institutes of Health (Li& Lumeng, 1984), and in MR/Har rats from the Harringtonderivation (Adams et al., 1991, 2001; Satinder, 1972). How-ever, unlike rat lines selected for high ethanol intake thatconsume high levels of ethanol in a variety of settings, suchas the alcohol-preferring (P) and high-alcohol-drinking(HAD) lines (Li et al., 1993), MR/Har rats often exhibit ahigh level of variability in the onset of heavy ethanol con-sumption (Adams, 1995; Adams et al., 1991). Moreover,MR/Har sometimes fail to initiate ethanol drinking in par-

ticular cage settings, although these settings do not lower anestablished high level of ethanol consumption (Adams etal., 2000). On the other hand, Maudsley nonreactive(MNRA/Har) rats (which were selected for low reactivity tomild stress) drink more moderately across a variety of con-texts. In all these studies, a continuous-access, home cage,two-bottle (10% ethanol and water) procedure was used tomeasure ethanol consumption. Whereas these measures canindicate overall ethanol intake, they do not measure directlythe ability of ethanol to reinforce behavior (Meisch, 1982).

Samson and his colleagues have found differences be-tween the home cage measure of ethanol consumption andoperant self-administration. In the operant self-administra-tion condition after initiation with the use of a sucrose-sub-stitution procedure (Samson, 1986), a shift in home cageethanol preference was observed (Tolliver et al., 1988).Also, differences in home cage drinking and ethanol rein-forcement, as measured in the operant procedure, have beennoted in inbred lines (Files et al., 1997b), alcohol-preferringand alcohol-nonpreferring selected lines (Files et al., 1997a,1998; Samson et al., 1998), and the high-alcohol-sensitiveand low-alcohol-sensitive selected lines (Files et al., 1996).

* Corresponding author. Tel.:

�

1-336-750-2626; fax:

�

1-336-750-2647.

E-mail address

: adamsn@wssu.edu (N. Adams).Editor: T.R. Jerrells

156

N. Adams et al. / Alcohol 26 (2002) 155–161

Thus, the following study was performed to examine self-administration in the MR/Har and MNRA/Har rats in theoperant self-administration paradigm for comparison withthe other selected lines studied in this procedure.

2. Materials and methods

2.1. Animals

Male rats from the Maudsley reactive (MR/Har) andMaudsley nonreactive (MNRA/Har) inbred strains bred atWinston-Salem State University were used [see Adams et al.(2001) for details]. At the age of 3 months, rats were trans-ferred to a vivarium at Wake Forest University, which is ap-proved by the Association for Assessment and Accreditationof Laboratory Animal Care (AAALAC). On arrival at WakeForest the rats were housed individually in stainless steelcages with food and water available ad libitum, except asnoted. Temperature and humidity were maintained to meetthe standards recommended in the

Guide for the Care andUse of Laboratory Animals

(Institute of Laboratory AnimalResources, Commission on Life Sciences, National ResearchCouncil, 1996). All experimental procedures were approvedby the Wake Forest University School of Medicine AnimalCare and Use Committee. Rats (

n

�

8 for each strain) had noprior testing or ethanol experience and ranged in age between87 and 102 days when protocols began. This age was compa-rable to the starting age of rats from selected lines in previousstudies in which this paradigm was used.

2.2. Apparatus

The operant chambers (MED Associates, St. Albans,VT) have been described previously in detail (Samson et al.,1998). For this study, one lever and dipper system locatedon the left-hand side of the chamber was used, with the otherlever removed from the chamber. The dipper presented 0.1 mlof fluid for 3 s when activated. All experimental events werecontrolled and monitored by a microcomputer operating un-der MED-PC software (MED Associates).

2.3. Procedure

On arrival at Wake Forest, the rats were handled andweighed daily for 3 days to adapt to the individual homecage setting. Next, for 3 consecutive days, rats received a10% (vol./vol.) ethanol (10E) solution as the only fluidavailable on the home cage. Then they received a two-bot-tle, home cage preference test between a 10E solution andtap water for 14 days. The rats’ daily intake of 10E and wa-ter and body weights were measured at the same time eachday. Each bottle was alternated from the previous day’s po-sition to avoid a position bias.

On completion of the preference test, operant trainingbegan. Table 1 summarizes the sequence and time line ofthe following procedures. The rats were first trained to pressthe lever with the use of a 20% (wt./vol.) sucrose (20S) so-lution in the dipper as the reinforcer. Access to water in the

home cages was restricted to 30 min per day after the operantsession to facilitate the dipper training for 6 days. Food wasnot restricted. During this period, the rats received two to threeovernight (16 h) training sessions in the operant chamber, dur-ing which a fixed ratio (FR) schedule of 1 (FR1) presented thesucrose solution. When the rats were consistently respondingduring daily 30-min sessions with 20S solution presentation,the sucrose concentration was reduced to 10% (i.e., 10S). Af-ter three sessions of 10S solution reinforcement, water restric-tion ended, and water was available ad libitum on the homecage for the remainder of the experiment. Over the next 20daily 30-min sessions, the percentage of the sucrose solutionto ethanol was decreased such that at the end of the initiation,10E in water was the solution presented after completion ofthe response requirement. This was the identical initiation pro-cedure used in prior studies with the selected lines (Samson etal., 1998; Table 1). During these sessions, the reinforcementschedule remained at FR1. Once the 10E solution was the so-lution presented, the FR schedule was gradually increased toFR4. The rats then received solution 5 days on an FR4 sched-ule with the ethanol concentrations at 10%, 15%, 20%, and30%, followed by five final sessions with a 10E solution pre-sented in the dipper. At the conclusion of the operant sessions,the rats received a second 14-day home cage preference test.One MNRA/Har rat failed to work for sucrose and was omit-ted from further testing.

2.4. Data analysis

Body weights, number of responses, and number of rein-forcements for each rat were recorded daily. The ethanol in-take was calculated as a function of body weight on the ba-

Table 1Experimental procedure

Condition No. of days

Home cage

10% Ethanol (10E) only fluid 310% Ethanol/water choice 14

Operant testing

Dipper training, 20% sucrose (20S) 1–2Overnight 20S 330 min, FR1, 20S 330 min, FR1, 10S 230 min, FR1, 10S/2E 230 min, FR1, 10S/5E 330 min, FR1, 10S/10E 230 min, FR1, 5S/10E 330 min, FR1, 2S/10E 230 min, FR1, 10E and 2S/10E alternating 530 min, FR1, 10E 330 min, FR2, 10E 330 min, FR4, 10E 530 min, FR4, 15E 530 min, FR4, 20E 530 min, FR4, 30E 530 min, FR4, 10E 5

Home cage

10E/water choice 14

FR

�

Fixed ratio.

N. Adams et al. / Alcohol 26 (2002) 155–161

157

sis of the number of reinforcements presented (grams ofethanol per kilogram of body weight). The Student

t

test,analysis of variance (ANOVA) designs, and Student–New-man–Keuls method were implemented to display the statis-tical significance with the use of a commercial statisticalpackage (SigmaStat, Jandel Scientific, San Rafael, CA).

3. Results

3.1. Home cage consumption

Ethanol consumption during the 3 days of forced expo-sure to a 10E solution was not different across strains (MR/Har

�

5.6

�

0.3 g/kg/day; MNRA/Har

�

6.3

�

0.2 g/kg/day) [

t

(14)

�

1.94,

P

�

.05]. However, at this time, MR/Har rats weighed significantly more than MNRA/Har rats(283.9

�

5.2 g and 259.7

�

5.8 g, respectively) [

t

(13)

�

3.03,

P

�

.01].During the initial home cage, two-bottle test, 10E pref-

erence scores and daily intake of absolute ethanol relativeto body weight (MR/Har

�

1.5

�

0.5 g/kg vs. MNRA/Har

�

1.7

�

0.3 g/kg) did not differ across strains (Fig. 1). Afterthe operant testing, both strains exhibited significant in-creases (from 19.1%

�

8.1% to 60.9%

�

5.3% in MR/Harand 16.7%

�

3.2% to 48.5%

�

5.0% in MNRA/Har) inethanol preference compared with that in the initial homecage preference test [

F

(1,29)

�

105,

P

�

.001] (Fig. 1). Asimilar increase occurred for daily ethanol intake (MR/Har

�

1.5

�

0.5 g/kg to 3.8

�

0.3 g/kg; MNRA/Har 1.7

�

0.3 g/kg to 3.3

�

0.4 g/kg) across sessions [

F

(1,29)

�

27.3,

P

�

.001].

3.2. Sucrose substitution initiation

During the initiation procedure, MNRA/Har rats generallyresponded at a higher level than MR/Har rats. Before ethanolwas added, MNRA/Har rats made significantly more re-sponses (65.3

�

8.0) than did MR/Har rats (37.9

�

3.4) whensucrose was the solution presented in the dipper [

t

(13)

�

3.3,

P

�

.01]. However, as ethanol was added, this difference inresponding diminished, so that the level of responding inMNRA/Har rats was only marginally higher than that in MR/Har rats until the sucrose was completely eliminated from thesolution. On the other hand, Fig. 2 shows that MNRA/Har ratsconsumed significantly more ethanol (.28

�

.04 g/kg), when a10% sucrose/2% ethanol (10S/2E) solution and a 10% su-crose/10% ethanol (10S/10E) solution (.85

�

.10 g/kg) waspresented, than did MR/Har rats, which consumed .16

�

.02g/kg and .48

�

.10 g/kg, respectively [

P

’s

�

.05]. This differ-ence between responding and ethanol intake was accountedfor by body weight, as the MNRA/Har rats weighed signifi-cantly less than the MR/Har rats (295.6

�

6.4 g and 352.4

�

9.6 g, respectively) during the initiation procedure [

t

(13)

�

4.93,

P

�

.001].

3.3. Operant self-administration

Both MR/Har and MNRA/Har rats exhibited low levelsof ethanol-maintained responding and intake during the 30-min self-administration periods after initiation (Fig. 3). TheMNRA/Har rats had a greater ethanol intake than that forMR/Har rats across all concentrations [

F

(1,13)

�

12.6,

P

�

.005]. Both strains showed increased ethanol intake as theconcentration increased [

F

(4, 13)

�

12.2,

P

�

.0001].However, the increase was greater in MNRA/Har rats as re-flected in a strain

�

concentration interaction [

F

(4, 13)

�

6.3,

P

�

.001]. Despite the increased intake at higher con-centrations, neither strain showed an increase in 10E solu-tion intake after exposure to higher ethanol concentrationswhen compared with findings for the initial 10E solutionpresentation.

Consistent with their greater ethanol intake, MNRA/Harrats made significantly more lever presses on the FR4schedule across the different ethanol concentrations com-pared with findings for MR/Har rats [

F

(1, 13)

�

11.3,

P

�

.01]. However, there was no effect of concentration on num-ber of lever presses, and thus the increased intake of ethanolresulted because the lever presses remained relatively con-stant as the concentration increased.

4. Discussion

That the MR/Har and MNRA/Har rat strains did not dif-fer in their home cage intake of a 10E solution was not con-sistent with previous findings (Adams et al., 1991, 2001). Inthose studies, in which rats were exposed to ethanol beforethe two-bottle, home cage test, the MR/Har strain of ratshad a higher preference and intake compared with findingsfor the MNRA/Har strain of rats. However, differences in

Fig. 1. Preference for 10% ethanol in male Maudsley reactive (MR) andMaudsley nonreactive (MNRA) rats during a 14-day period of two-bottlechoice before and after the sucrose-substitution and ethanol-concentration-manipulation procedures. Strains did not differ from each other on ethanolpreference; both strains showed a significant increase (P � .001) from thefirst 14-day period to the second 14-day period.

158

N. Adams et al. / Alcohol 26 (2002) 155–161

ethanol consumption in the MR/Har rats are affected bysubtle differences in protocol across laboratories (e.g., Ad-ams et al., 1991 vs. Overstreet et al., 1993) and across stud-ies within laboratories (Adams et al., 2000). Thus, the lackof any difference in home cage intake in the present studymay be related to the difference in setting and protocol used.Although ethanol intake was low during the initial period ofhome cage continuous access to ethanol, both strains mark-edly increased their ethanol intake after the operant, ethanolself-administration portion of the experiment. Thus, this op-erant, limited-access exposure to ethanol seems to havebeen sufficient to alter the ethanol consumption of the ratsin the home cage setting. However, without a control groupthat did not receive the self-administration procedure, theeffects of age or retesting as contributors to the increased in-take during the second period of home cage access to etha-nol cannot be discounted. This control would be importantin future research as during the initial home cage, two-bottletest the rats were younger and weighed considerably less incomparison with the rats in previous studies in which theMaudsley strains were used in home cage settings.

Perhaps the most significant finding of this study was thelow levels of ethanol self-administration observed. The MR/Har rats showed little to no ethanol self-administration, andthe MNRA/Har rats showed a low, but reliable level of eth-anol intake that was similar to that observed in alcohol-non-preferring (NP) rats (Samson et al., 1998). That is, the

MNRA/Har rats were marginally initiated. However, thelevel of ethanol intake at the 10E level after the concentra-tion manipulation was less than 0.2 g/kg, which seems to in-dicate that measurable blood ethanol levels were notachieved. In addition, even though there was an increase inethanol intake in both strains as the ethanol concentrationincreased after the sucrose-substitution procedure, this wasa result of no change in the number of responses or patternof responding as the concentration increased. On the basisof prior studies with the use of these procedures with otherlines of rats (Samson, 1986; Samson et al., 1998), thisseems to indicate that ethanol intake was minimal at anyethanol concentration presented, as well as that the ratsmade no attempt to compensate for the increased concentra-tion. Also, neither strain showed an increase in ethanol self-administration at the second exposure to 10E solution afterconcentration manipulation (see Fig. 3). Both an increasedamount and a change in the pattern of ethanol intake duringthe second 10E solution self-administration have been re-ported following this initiation procedure (Samson, 1986;Samson et al., 1998).

The results showing that MR/Har rats failed to initiateself-administration of ethanol was partly surprising. Thereare a number of previous findings supporting the suggestionthat MR/Har rats might exhibit moderate to high levels ofself-administration of ethanol. First, their high level of etha-nol intake in the home cage in some settings is comparable

Fig. 2. Mean ethanol intake (in grams per kilogram of body weight) for Maudsley reactive (MR) and Maudsley nonreactive (MNRA) rats during the sucrose-substitution protocol and the period of manipulation of the response schedule from fixed ratio (FR) 1 (FR1) to FR4 with 10% ethanol (10E) as the reinforcer.Asterisks indicate significance at P � .05, and double asterisks indicate significance at P � .01. 10S/2E � 10% sucrose/2% ethanol solution; 10S/5E � 10%sucrose/5% ethanol solution; 10S/10E � 10% sucrose/10% ethanol solution; 5S/10E � 5% sucrose/10% ethanol solution.

N. Adams et al. / Alcohol 26 (2002) 155–161

159

to that of alcohol-preferring rats, such as the P and HADlines (Li et al., 1993), and unpublished observations (N. Ad-ams & D. A. Blizard, 1991) indicate that MR/Har ratsachieve pharmacologically significant blood ethanol levels(40–50 mg/dl) in home cage settings with free access to eth-anol. Second, MR/Har rats have been reported to exhibitmotor activation after injections of low doses of ethanol(Erickson & Kochhar, 1985). However, in that study MRrats from the National Institutes of Health stocks (MR/N)were used, and they have been separated from the MR/Harrats since the mid-1960s. Nevertheless, comparisons ofthese two lines of MR/Har show that they do not differ onthe original selection criterion (Blizard et al., 1982). Finally,the MR selection criterion for stress susceptibility or “emo-tionality” supported the suggestion that ethanol might be re-inforcing according to a stress-reduction hypothesis.

On the other hand, there are a number of reasons thatmight explain the failure of MR/Har rats to initiate self-administration of ethanol. As noted previously, results ofmany studies of ethanol intake in MR/Har rats indicate ahigh degree of variability in their propensity to consumelarge amounts of ethanol (Adams, 1995; Adams et al., 1991,2001). Small differences in environmental factors, such asthe type of housing before ethanol exposure (Adams & Old-ham, 1996), method of food delivery during the period ofethanol exposure (Adams et al., 2000), and whether ratshave forced exposure to ethanol before a period of choice(Adams et al., 2001), have major effects on ethanol con-sumption in MR/Har rats. Thus, it is

not

unexpected that

MR/Har rats failed to exhibit an ethanol self-administrationpattern consistent with findings obtained from home cagestudies in a different laboratory. The nature of MR/Har ratsbeing stress sensitive or reactive to mildly novel environ-ments (Blizard, 1981; Broadhurst, 1975) supports the sug-gestion that a protocol that is sensitive to distractions maynot reveal the MR/Har ethanol phenotype as well as it mightin less environmentally sensitive rats. Finally, it is impor-tant to note that all manipulations described above have amuch stronger effect on male MR/Har rats than on femaleMR/Har rats. Thus, female MR/Har rats, which generallydrink more ethanol than male MR/Har rats (and with lessvariability) across many situations (Adams, 1995; Adams etal., 1991, 2000, 2001), may be appropriate subjects forstudying ethanol-seeking behavior in the operant paradigm.

Another reason that MR/Har rats may not have initiatedethanol self-administration is reflected by the difference inethanol intakes that occurred between MR/Har and MNRA/Har rats during the sucrose-fading protocol. The MNRA/Har rats had a consistently greater intake of ethanol thanthat of the MR/Har rats during the presentation of the su-crose/ethanol mixtures, although they were only marginallyhigher at the 10S/5E, 5S/10E, and 2S/10E concentrations.At the 10S/10E concentration, MNRA/Har rats had nearlydouble the ethanol intake of the MR/Har rats. At that time inthe procedure, the MNRA/Har rats most likely reachedpharmacologically active blood ethanol levels by consum-ing an average of 0.8 g/kg in the first 15 to 20 min of the 30-min session (Czachowski et al., 1999). It is assumed that formaintenance of the lever pressing response, based on the re-inforcing qualities of ethanol to occur, ethanol intakes dur-ing initiation must pair some physiological effects of theconsumption with the pressing. The MR/Har rats, on the otherhand, consumed only an average of 0.4 g/kg, spread out over abetter part of the 30-min session. This pattern of intake maynot have been great enough to produce the pharmacologicalactivity required to develop ethanol self-administration.

Another possible reason that the MNRA/Har rats ac-quired some degree of self-administration in comparisonwith that observed for the MR/Har rats is that MNRA/Harrats have a different avidity for sucrose. The MNRA/Harrats consume more sucrose than do MR/Har rats at 1.5%and 3% sucrose concentrations, although both strains ex-hibit nearly identical (95%) preference ratios for these solu-tions (unpublished observations, N. Adams, 2001). As ob-served in the current study, MNRA/Har rats respondedreliably more during the 10S solution sessions than did theMR/Har rats. The MNRA/Har rats also showed a steep de-cline in responding as ethanol was added to the sucrose so-lution, whereas responding of MR/Har rats remained thesame for 10S, 10S/2E, and 10S/5E concentrations (albeit ata lower level than the responses of MNRA/Har rats to thesesolutions). These differences in avidity for sucrose seem toindicate that the standard sucrose-substitution protocol usedin the current study may not have been an optimal protocolfor initiating ethanol self-administration in the MR/Har

Fig. 3. Mean ethanol intake (in grams per kilogram of body weight) forMaudsley reactive (MR/Har) and Maudsley nonreactive (MNRA/Har) ratsduring manipulation of the ethanol concentration [fixed ratio (FR) 4response schedule]. The MNRA/Har rats consumed significantly more eth-anol than did MR/Har rats overall and at each concentration (P � .01)except for the return to 10E (the last comparison). 10E, 15E, 20E, and 30E �10%, 15%, 20%, and 30% ethanol solutions, respectively.

160 N. Adams et al. / Alcohol 26 (2002) 155–161

strain of rats. It is possible that MR/Har rats would developethanol-reinforced behavior under a different initiationschedule, in which their lower sucrose intake was taken intoaccount. Perhaps more extended time at the 10E/5S concen-tration would have led to the “successful” initiation of etha-nol self-administration, but extending the number of dayswith a given sucrose/ethanol solution has not been success-ful in the training regimen across past studies (unpublishedobservations, H. H. Samson, 1989). Because one major pur-pose for this study was to compare the Maudsley strains toalcohol-preferring and alcohol-nonpreferring strains used inother studies, it was critical to use the same protocol as usedin those studies. Future studies with MR/Har rats that alterthe initiation procedure might be of value, as it was foundthat ethanol self-administration could be initiated in the NPrat (Samson et al., 1989).

A main objective of the present study was to compare theethanol self-administration of the Maudsley rats with theother selected rat lines that have been tested with this proto-col during the past several years. Strains that were geneti-cally selected to be high or low consumers of ethanol incontinuous home cage settings, including the P and NPlines, both replicate lines of the HAD and low-alcohol-drinking (LAD) lines, and the alcohol-accepting (AA) andalcohol-nonaccepting (ANA) lines, have been studied withthe use of this protocol (Samson et al., 1998). Results ofthese studies showed that, although there is a correlation be-tween high ethanol intake in the home cage and in the oper-ant setting, there are substantial differences among ethanol-preferring strains (Files et al., 1998; Samson et al., 1998).Thus, the phenotype for high levels of ethanol consumptionin the home cage includes different subcomponents that arerevealed by using the operant self-administration proce-dures. The results of this study, showing a minimal level ofethanol self-administration in MR/Har rats, indicate that thehigh ethanol intake in MR/Har rats observed in some homecage settings may represent a different ethanol phenotypethan that observed for the home cage drinking in P andHAD rats. These latter rat strains, which were selected forethanol preference, drink high levels of ethanol in a varietyof settings and readily self-administer ethanol in the proto-col used in the current study. Therefore, although the MR/Har rats may not be an appropriate model for studying etha-nol-seeking behavior in the present paradigm, they may pro-vide interesting insights regarding the interaction of geneticvulnerability with sensitivity to subtle environmental influ-ences on ethanol consumption.

Acknowledgments

This work was supported by a grant from NIGMS-MBRS-008040 to N. A. and grants P50 AA11997, R37AA06845, and KO5 AA00142 from the National Instituteon Alcohol Abuse and Alcoholism to H. H. S. We wouldlike to thank Ann Chappell and Charles Denning for theirhelp in the training phase and for data collection.

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