1.
Kulkosky, P.J.; Allison, T.G.; Carr, B.A. Angiotensin II reduces alcohol intake and choice in water- or food-restricted rats . Alcohol: An International Biomedical Journal, 13(4):359-363, 1996 .

Two experiments were conducted to assess the effects of administration of the neuropeptide and hormone angiotensin II (A-II) on ethanol intake and choice. First, 18 male Wistar rats were water deprived for 23 hours and given access to 5 percent w/v ethanol for 30 minutes, followed by 30 minutes of access to water; food was ad lib. Following adaptation to this schedule, rats were randomly assigned to receive an intraperitoneal injection of 0, 100, or 200 micrograms/kg o f A-II at either -30 or 0 minutes prior to ethanol access. Each A-II injection decreased ethanol intake only if injected immediately before access; water and food intake were unaffected. Secondly, rats were given food daily at 2 percent of body weight wit h ad lib water and randomly assigned to receive intraperitoneal saline or 200 micrograms/kg of A-II prior to presentation of a choice of ethanol or water for 1 hour. A-II reduced ethanol intake and increased water intake at 0 to 30 minutes after injection . The results confirm previous reports of inhibition of alcohol consumption by peripheral A-II, and indicate a temporal constraint on A-II's effect, which is consistent with a role as a short-term satiety factor. 35 Ref.

2.
Kulkosky, P.J. Neuropeptidergic control of ethanol intake . Journal of Toxicology - Toxin Reviews, 15(4):341-351, 1996 .

This article reviews studies on the modulation of ethanol intake by neural peptides found in brain and gut tissues. Experiments have shown that the oral consumption of ethanol solutions is potently reduced by injection s of sulfated cholecystokinin octapeptide, tetradecapeptide bombesin, angiotensin, and the opioid receptor blockers naloxone and naltrexone. Alcohol intake is increased by vasoactive intestinal peptide, neuropeptide Y, and galanin, and relapse in alcoholi cs is associated with increases in blood levels of the opioid peptide beta-endorphin. Ethanol intake is increased by specific neuropeptide receptor blockers, which also prevent injected cholecystokinin and bombesin from inhibiting ethanol intake. Naltrexo ne was recently approved by the Food and Drug Administration for wider use in the clinical treatment of alcoholism. Neuropeptidergic regulation of alcohol consumption and innovative therapies are supported by these findings. 37 Ref.

3.
Kulkosky, P.J.; Carr, B.A.; Flores, R.K.; LaHeist, A.F.; Hopkins, L.M., Conditioned taste aversions induced by alcohol and lithium in rats selectively bred for ethanol neurosensitivity . Alcoholism: Clinical and Experimental Research, 19(4):945-950, 1995 .

Rats that were selectively bred for differences in alcohol-induced sleep time (alcohol neurosensitivity) were tested for differences in formation and extinction of alcohol- and LiCl-induced conditioned taste aversions. Male rats bred for high, control, or low alcohol sensitivity (HAS, CAS, and LAS rats, respectively) were deprived of water and given daily 30 min access to water for a baseline period of 7 days. Rats were then given a novel O.125 percent sodium saccharin solution, followed by an intraperitoneal injection of either saline, 2 g/kg of ethanol (at 10 percent w/v), or 50.9 mg/kg of LiCl (0.15 M) on 3 conditioning days. Each saccharin exposure was followed by a recovery day of access to water. The ethanol-indu ced saccharin aversion extinguished more rapidly in LAS rats than in CAS or HAS rats (p < 0.05), but LiCl conditioned equivalent aversions in each group. Also, ethanol injection results in large differences in observed resting behavior in these rats (H AS > CAS > LAS), but LiCl injection produced no reliable group differences in resting. The weaker alcohol-induced taste aversion in LAS rats accords with their previously measured higher oral consumption of alcohol (Kulkosky et al., Alcoholism 17: 5 45-551, 1993) and the idea that alcohol intake is limited by an expectancy of postingestive consequences. The weaker ethanol-induced aversion in LAS rats reflects selective breeding of an alcohol-specific trait and not a general difference in aversive con ditioning or chemical neurosensitivity. 39 Ref.

4.
Carr, B.A.; Ballou, J.D.; Marrinan, D.A.; Kulkosky, P.J. Desmethionine-bombesin receptor antagonist blocks bombesin-induced inhibition of alcohol intake . Alcohol: An International Biomedical Journal, 11(2):125-131, 1994 .

(D-Phe super 6, Des-Met super 14)bombesin(6-14), ethyl amide (D-BN) is a specific, competitive receptor antagonist of bombesin, a neuropeptide that inhibits alcohol and food intake. The effects of IP injected D-BN (4- 400 microg/kg) were tested on bombesin-induced (4 microg/kg) reduction of caloric intake. In the first experiment, ad lib-fed female and male rats (Ns=18) were deprived of water for 23 h, injected with peptides or saline in randomized sequences of doses, and immediately given access to 5 percent w/v ethanol for 30 min, followed by 30 min of water. In a second experiment, male rats (N=10) were injected with the antagonist at 10 or 20 min prior to bombesin injection and alcohol access, and behaviors were observed and quantified once a minute with an instantaneous time-sampling technique. D-BN injection blocked the bombesin-induced reduction in alcohol intake (equal to or more than 40 microg/kg) and food intake (equal to or more than 200 microg/kg). When injected 20 min prior to access, D-BN alone (200 microg/kg) initially elevated alcohol drinking and later increased feeding behaviors and decreased resting, relative to saline injection. Results indicate bombesin-induced reduction of alcohol intake depe nds on a specific peptidergic receptor process, and endogenous bombesin-like peptide could act physiologically to elicit satiation with ethanol and food. 25 Ref.

5.
Carr, B.A.; Ballou, J.D.; Snell, J.C.; Kulkosky, P.J. MK-329 blocks the inhibition of alcohol intake by CCK-8 . Peptides, 14(6):1193-1197, 1993 .

The effects of cholecystokinin octapeptide (CCK-8), which reduces alcohol intake, preference, and blood levels in rats, and of MK-329 (L-364,718 or Devazepide), which acts at peripheral cholecystokinin (CCK sub A) rece ptors to antagonize the effects of CCK-8, were studied in male and female Wistar rats. After 8 days of adaptation, rats received 1 mL/kg intraperitoneal injections of MK-329 at concentrations of 100 microg/kg, 200 microg/kg, and 400 microg/kg 30 minutes p rior to IP injections of sulfated CCK-8. The animals then received a 5 percent w/v solution of ethanol for 30 minutes, followed by water for 30 minutes. The following results of the study were seen: (1) significant suppression of alcohol and food intak e by CCK-8; (2) reduced suppression of alcohol intake and food intake by CCK-8 with all doses of MK-329; (3) increased alcohol intake with MK-329 alone at a dose of 400 microg/kg; and (4) increased food intake with MK-329 alone at 200 microg/kg in females and at 200 micro/kg in males. It is concluded that the effects of CCK-8 on alcohol and food intake are dependent on specific, peripheral CCK sub A receptors, with satiation reflecting an endogenous functional interaction of CCK-8 with these receptors. 48 Ref.

6.
Kulkosky, P.J.; Clayborne, Y.J.; Sandoval, S.L. Cholecystokinin and bombesin inhibit ethanol and food in rats selectively bred for ethanol sensitivity . Alcoholism: Clinical and Experimental Research, 17(3):545- 551, 1993 .

Cholecystokinin octapeptide (CCK-8) and bombesin tetradecapeptide (BBS- 14) are brain-gut neuropeptides shown to inhibit intake and choice of alcohol solutions and foods in a variety of species. Recently, Draski and co lleagues selectively bred strains descended from N/Nih outbred Norway rats that differ in sleep time after injection of ethanol. The intake of 5 percent w/v ethanol, food, and water was measured in these rats with high, low, and control alcohol sensitivit y (HAS, LAS, and CAS), after intraperitoneal injection of randomized sequences of doses of CCK-8 or BBS-14 (0-8 microgram/kg). During baseline adaptation to water deprivation-induced consumption of alcohol, LAS rats consumed reliably more ethanol than HAS or CAS rats. Injection of CCK-8 or BBS- 14 significantly and equivalently suppressed intake of ethanol and food at 30 min after presentation in each group of rats. Water intake and food intake at 30-60 min following alcohol access was not affected by pri or injection of either neuropeptide. Large differences in alcohol neurosensitivity (HAS greater than CAS greater than LAS) were observed in these rats' resting behavior for 1 hr after intraperitoneal injection of 1 g/kg of ethanol. These selectively bred alcohol neurosensitivity/differences cannot be explained by corresponding differences in sensitivity to the inhibitory behavioral effects of CCK8 or BBS-14. However, differences in alcohol intake and resting behavior do correspond to artificially selected sensitivities to ethanol's hypnotic effect. 43 Ref.

7.
Kulkosky, P.J.; Sanchez, M.R.; Marrinan, D.A. Bombesin reduces alcohol choice in nutritive expectancy and limited- access procedures . Alc ohol: International Biomedical Journal, 9(2):123-127, 1992 .

Bombesin is a bioactive tetradecapeptide found in nerves of the brain and gut and previously shown to inhibit intake of ethanol in forced- choice, one-bottle tests in water-deprived rats. In the present experiments, in traperitoneal bombesin (4-100 micrograms/kg) reduced selection of alcohol in two-bottle choice tests with water. In an application of the "nutritive expectancy" procedure, weight-reduced rats received access to 4 percent w/v ethanol and water. B ombesin injection suppressed the intake of ethanol, but not of water, in rats with prior ethanol experience. In an application of the "limited access" procedure, nondeprived rats received access to 6 percent w/v ethanol and water in nonhome cage s during either the light or the dark phase of a 12:12 h lighting cycle. Bombesin injection lowered the intake of ethanol, but not of water, in both phases of the lighting cycle and in both sexes. Water deprivation is not necessary for bombesin to inhibit alcohol intake and this effect cannot be explained by hypodipsia, nonspecific debilitation, or conditioned aversion. Endogenous bombesin-like neuropeptides may specifically reduce choice of alcohol by signaling satiation with ethanol. 56 Ref

8.
Dietze, M.A.; Kulkosky, P.J. Effects of caffeine and bombesin on ethanol and food intake . Life Sciences, 48(19):1837-1844, 1991 .

The methylxanthine caffeine and ethyl alcohol are widely used and powerful psychotropic drugs, but their interactions are not well understood. Bombesin is a brain-gut neuropeptide which is thought to function as a neur ochemical factor in the inhibitory control of voluntary alcohol ingestion. The effects of combinations of intraperitoneal (i.p.) doses of caffeine (CAF, 0.1-50 mg/kg) and bombesin (BBS, 1-10 microg/kg) on 5 percent w/v ethanol solution and food intake wer e assessed in deprived rats. Deprived male and female Wistar rats received access to 5 percent ethanol or Purina chow for 30 minutes after i.p. injections. In single doses, CAF and BBS significantly decreased both ethanol and food consumption, at 50 mg/kg and 10 microg/kg, respectively. CAF and BBS combinations produced infra- additive, or less-than-expected inhibitory effects on ethanol intake, but simple additive inhibitory effects on food intake. This experimental evidence suggests a reciprocal blockin g of effects of CAF and BBS on ethanol intake but not food intake. Caffeine, when interacting with bombesin, increases alcohol consumption beyond expected values. Caffeine could affect the operation of endogenous satiety signals for alcohol consumption. 3 7 Ref.

9.
Kulkosky, P.J.; Foderaro, M.A..; Sandoval, S.L.; Cesar, S.S.; Marrinan, D.A. Cholecystokinin-induced satiation with ethanol: Effects of li ghting cycle and limited access procedures . Alcohol: An International Biomedical Journal, 8(3):223-227, 1991 .

The effects of cholecystokinin (CCK), a brain-gut neuropeptide and hormone, and the phase of lighting cycle on alcohol intake in rats were investigated using a limited access procedure (LAP) technique. Two groups of 12 male rats each were maintained in either normal or reversed 12:12 L:D lighting cycle and simultaneously given 40 minutes' access to 6 percent w/v ethanol and water in nonhome cages. After adaptation to this procedure, CCK octapeptide (0.5-16 ug/kg) was i njected IP prior to access to fluids. During LAP, CCK reduced alcohol intake and increased water intake more potently in the dark phase. These effects of CCK were more reliable when the design was replicated, which suggests the importance of acquired expe ctancies for the development of CCK's actions. CCK more effectively reduced alcohol intake in LAP, than in a 23.3-h water-deprivation procedure for inducing alcohol intake in a 2-bottle choice test with water. However, CCK was less so effective in LAP, th an in the water-deprivation procedure when alcohol was presented alone in a 1-bottle test. The alcohol satiation effect of CCK is independent of prior deprivation and not an artifact of thirst reduction, debilitation, or conditioned aversion, because CCK strongly increased water intake in the limited access procedure, and ethanol preference remained robust after experience with CCK. CCK is thought to operate endogenously as a specific factor in satiation with ethanol. 23 Ref

10.
Kulkosky, P.J.; Holst, W.E.; Smith, W.G.; Dietze, M.A. Effect of CCK-8 on intake of caffeine, ethanol, and water . Bulletin of the Psychon omic Society, 29(5):441-444, 1991 .

The effects of cholecystokinin octapeptide (CCK-8), which is a gut hormone and neural peptide that inhibits food intake, on consumption of caffeine, ethanol, and water were studied in female Wistar rats that were admin istered solutions of caffeine, ethanol, or water after injection of CCK-8. The study results indicated that CCK-8 reduced consumption of the ethanol solution and decreased associated feeding behaviors but did not reduce intake of the caffeine solution or of water. Food intake decreased and activity level increased following consumption of the caffeine solution. It is concluded that CCK-8 specifically reduces ethanol consumption but not caffeine ingestion. The anorexias induced by CCK-8 and caffeine appear to be nonadditive and distinct. 16 Ref.

11.
Kulkosky, P.J.; Sanchez, M.R.; Foderaro, M.A.; Chiu, N. Cholecystokinin and satiation with alcohol . Alcohol, 6(5):395-402, 1989 .

Release of the brain-gut peptide cholecystokinin (CCK) is stimulated by intragastric instillation of ethanol, and peripheral administration of CCK inhibits ethanol consumption. To assess the temporal specificity of the inhibitory effect of CCK on alcohol intake, water-deprived rats were given 5 percent ethanol at 20, 10, or 0 min after intraperitoneal injections of CCK octapeptide. Delaying access to ethanol for 20 min prevented a significant effect of CCK on intake. C CK's temporally constrained inhibitory action on alcohol consumption is consistent with an ethanol satiation effect. To test the motivational specificity of CCK's effect on fluid intake, rats were allowed a 2-bottle choice of 2 percent ethanol and water a fter CCK injections. Ethanol solution intake was suppressed by CCK, and total water intake was unaffected. The putative alcohol satiation action of CCK is appropriately specific to ethanol solution in free-choice tests. Hungry, but not fluid-deprived rats that were either ethanol experienced or naive received a 2-bottle choice of 4 percent ethanol or water after CCK or saline injections. CCK again specifically inhibited ethanol intake, but this effect required prior ethanol experience. Doses of CCK and na loxone, an opioid receptor blocker, combined to inhibit ethanol intake in an infra-dose- additive manner in water-deprived rats. CCK may act endogenously, in part on opioid receptor-mediated processes, as a preabsorptive satiety signal of ethanol. The ful l expression of this action appears to depend on prior conditioning of nutritive expectancy of the postingestive effects of alcohol. 63 Ref.

12.
Kulkosky, P.J.; Doyle, J.S.; Cook, V.I.; Glazner, G.W.; Foderaro, M.A. Vasoactive intestinal peptide: Behavioral effects in the rat and ha mster . Pharmacology, Biochemistry, and Behavior, 34(2):387-393, 1989 .

The behavioral effects of intracerebroventricular (ICV) injection of the brain-gut peptide vasoactive intestinal peptide (VIP) were quantified with a behavioral sampling technique in home-caged nondeprived male and fem ale albino rats and golden hamsters. ICV VIP sex-dependently decreased observed resting behavior during 1 hour after injections in both rats and hamsters at 0.1 to 10.0 micrograms. Grooming behavior was increased in hamsters, and rearing and standing beha viors were increased in rats, sex dependently at VIP doses that decreased resting. Drinking behavior was suppressed in rats by VIP at 10.0 micrograms. Intraperitoneal (IP) VIP (100.0 micrograms/kg) increased 5 percent ethanol intake and decreased eating b ehavior in fluid-deprived male rats. The increase in ethanol intake produced by IP VIP was prevented by IP cholecystokinin octapeptide (CCK 4.0 micrograms/ kg). VIP potently controls resting and ingestive behaviors, suggesting a role for this neuropeptide , along with CCK, in the feedback regulation of rodent behavior. 41 Ref.

13.
Peniston-E-G; Kulkosky-P-J. alpha-theta Brainwave training and beta-endorphin levels in alcoholics. . Alcoholism: Clinical and Experimenta l Research, 13(2):271-279, 1989. .

An alpha-theta brainwave biofeedback training program was applied as a novel treatment technique for chronic alcoholics. Following a temperature biofeedback pretraining phase, experimental subjects completed 15 30-min sessions of alpha-theta biofeedback training. Compared to a nonalcoholic control group and a traditionally treated alcoholic control group, alcoholics receiving brainwave training (BWT) showed significant increases in percentages of electroencephalogram ( EEG) record in alpha and omega rhythms, and increased alpha rhythm amplitudes. Alcoholics receiving BWT showed a gradual increase in alpha and theta brain rhythms across the 15 experimental sessions. These experimentally treated alcoholics showed sharp r eductions in self- assessed depression (Beck's Depression Inventory) compared to the control groups. Alcoholics receiving standard medical treatment ( abstinence, group psychotherapy, antidepressants) showed a significant elevation in serum beta-endorphin levels at the conclusion of the experiment. This neuropeptide is an index of stress and a stimulant of caloric (e.g., ethanol) intake. Application of brainwave treatment, a relaxation therapy, appears to counteract the increase in circulating beta-endorp hin levels seen in the control group of alcoholics. 13-Month followup data indicate sustained prevention of relapse in alcoholics that completed alpha-theta brainwave training. 78 Ref.

14.
Glazner-G-W; Cannon-R-L; Kulkosky-P-J. Effect of bombesin on behaviors associated with ethanol satiation and blood ethanol levels. . Alcoh ol, 5(4):325-330, 1988. .

The behavioral specificity and physiological significance of bombesin-induced inhibition of ethanol intake were assessed in water- deprived rats. The behavioral display accompanying suppression of 5 percent ethanol int ake by bombesin tetradecapeptide (BBS-14, 1-4 microg/ kg) was measured with an instantaneous time-sampling technique. Blood ethanol levels were measured after peripheral BBS-14 and bombesin nonapeptide (BBS-9) administration, and after either oral self- a dministration or peripheral injection of ethanol. The display accompanying BBS-14-reduced ethanol consumption differed from control in that less drinking and feeding behaviors were observed and resting increased, dose-dependently. The typical behavioral s equence of ethanol satiation was observed in all conditions. Both BBS-14 and -9 reduced blood ethanol levels when oral intake was suppressed, and BBS-14 did not affect blood ethanol levels or elimination rate when ethanol was injected. The results are com patible with an hypothesis of a functional role for endogenous bombesin-like peptides and receptors in a neuropeptide control of ethanol intake and energy balance. 27 Ref.

15.
Kulkosky-P-J; Glazner-G-W. Dose-additive inhibition of intake of ethanol by cholecystokinin and bombesin. . Alcoholism: Clinical and Exper imental Research, 12(2):277-281, 1988. .

Cholecystokinin (CCK) and bombesin (BBS) are neuropeptides of the brain and gut which have been shown to inhibit intake of ethanol. CCK octapeptide and BBS tetradecapeptide were injected intraperitoneally in both singl e doses and combinations of doses to determine interactions of the two peptides in the control of consumption of ethanol. Water- deprived rats were given access to 5 percent w/v ethanol for 30 min, followed by a 30-min access to water, daily. One minute b efore presentation of ethanol, rats were injected with either saline or one of ten peptide solutions (three of CCS alone, three of BBS alone, and four combinations of both). Results from the injections of single peptides were used to determine predicted i nhibitions of the peptide combinations, assuming perfect additivity of doses. None of the actual values of inhibition of intake of ethanol by peptide combinations differed significantly from its predicted additive value. Endogenous CCK-like and BBS-like p eptides may suppress intake of ethanol by an additive mechanism of inhibition. 44 Ref.

16.
Kulkosky-P-J; Sanchez-M-R; Glazner-G-W. Cholecystokinin octapeptide: Effect on the ethogram of ethanol consumption and blood levels in the rat. . Physiological Psychology, 14(1/2):23-30, 1986. .

The inhibitory effect of peripheral injection of cholecystokinin octapeptide (CCK-8) on ethanol consumption was characterized by constructing an ethogram of ethanol consumption. Rats deprived of water for 23 hours rece ived 45-minute access to five percent weight to volume ethanol followed by 15-minute access to water. During ethanol access, observations of behavior were made at tone-cued one-minute intervals and classified into categories of ethanol drinking, feeding, standing, grooming, resting, and other behaviors. Rats injected with CCK-8 significantly reduced ethanol consumption and total observed feeding behavior, but no other behavioral changes were found. Rats then received, on a daily basis, 30-minute access to five percent ethanol followed by 30 minutes of water. Rats were injected with CCK-8 or saline, ethanol was presented, and blood samples were taken and assayed for ethanol. Blood ethanol and ethanol consumption were significantly reduced by CCK-8. These f indings support the hypothesis that CCK-8 may be an endogenous factor in ethanol satiation. 20 Ref.

17.
Kulkosky-P-J. Brain-gut neuropeptides and the limitation of ethanol consumption. . Neuroscience and Biobehavioral Reviews, 9(2):179-190, 1 985. .

Recent studies showing powerful control of ingestive behavior by certain peptides known to be present in both brain and gut tissues are reviewed. These "brain-gut neuropeptides" are thought to constitute endo genous factors that are responsible for the normal regulation of food intake. The potential for a role by these peptides in the limitation of ethanol intake, which shares several features with the control of food intake, is explored. The putative satiety role of the neuropeptides cholecystokinin and bombesin, and other brain-gut peptides, is described. Data from studies of rat and hamster ethanol consumption are used to illustrate the conclusion that voluntary ethanol intake is partially controlled as a f unction of the energy ethanol provides and the rate of its utilization. The possibility of neuropeptide influence on ethanol intake is discussed in light of findings that cholecystokinin and bombesin inhibit ethanol consumption in the rat. It is concluded that if neuropeptides are demonstrated to modulate ethanol intake by eliciting satiety, this finding may be useful in identifying and understanding the endogenous factors that regulate human alcohol intake and will suggest possible peptide-based therapeu tic interventions to control alcohol abuse and alcoholism. 212 Ref.

18.
Kulkosky-P-J. Effect of cholecystokinin octapeptide on ethanol intake in the rat. . Alcohol, 1(2):125-128, 1984. .

The effect of administration of cholecystokinin octapeptide (CCK-8) on water and ethanol solution intake was examined to determine if CCK-8 specifically controls ethanol intake in the rat. Water-deprived male Charles R iver Wistar rats received 3 percent, 6 percent, or 9 percent ethanol solution or water for 30 minutes daily. Intraperitoneal injection of CCK-8 (2.0 to 4.0 micrograms/kg) significantly and specifically inhibited ethanol intake, but not water intake. The f indings suggest that the control of ethanol ingestion by CCK-8 reflects an endogenous action of cholecystokinin in the short-term regulation of caloric intake. 40 Ref.

19.
Kulkosky-P-J; Chavez-M-R. Sulphated cholecystokinin octapeptide inhibits ethanol consumption in the rat. . Alcohol, 1(5):409-412, 1984. .

The mechanism of ethanol intake inhibition by peripherally administered cholecystokinin octapeptide (CCK-8), was investigated. Rats deprived of water for 23 hours received access to 5 percent ethanol solution for 30 mi nutes daily. Intraperitoneal injection of sulphated CCK-8 (2.0 to 16. 0 microg/kg) significantly inhibited ethanol consumption, but injection of desulphated CCK-8 did not affect ethanol consumption. These results confirm a previous report that CCK-8 suppr esses ethanol intake, and indicate that inhibition of ethanol consumption by CCK-8 depends on sulphation of its tyrosyl residue. This chemical specificity of action of CCK-8 is also characteristic of other known behavioral and physiological effects of per ipherally administered cholecystokinin-like peptides. The findings strengthen the idea that endogenous cholecystokinin is a potential modulator of ethanol consumption. 33 Ref.

20.
Kulkosky-P-J. Ethanol selection in wild-trapped agouti and laboratory albino Norway rats (Rattus norvegicus). . Physiol. Behav., 26: 677-6 80, 1981. .

Alcohol solution preferences of wild-trapped agouti Norway rats (n = 5, 4 females) and Wistar albino Norway rats (n = 5, 4 females; weight matched at about 125 g.) were compared in an ad lib, non-deprived 2- bottle cho ice of water or alcohol (1 to 17 percent w/v; increased 1 percent on consecutive days). Wistar rats showed their characteristic preference for low alcohol concentrations (3 percent) and strong avoidance of high alcohol concentrations. Wild rats showed onl y a weak aversion for high alcohol concentrations and no reliable preference for any alcohol solution to water. Results are discussed in terms of the previously observed higher metabolism, larger adrenal glands and relative inflexibility of wild rats.

21.
KULKOSKY-P-J; ZELLNER-D-A; HYSON-R-L. ETHANOL CONSUMPTION OF RATS IN INDIVIDUAL, GROUP, AND COLONIAL HOUSING CONDITIONS. . PHYSIOL. PSYCHO L., AUSTIN, TX, 8: 56-60, 1980. .

NINE MALE AND 9 FEMALE LONG-EVANS RATS WERE HOUSED IN A GROUP CAGE (3 MALES AND 3 FEMALES), IN A NATURALISTIC COLONIAL HABITAT (3 MALES AND 3 FEMALES) OR IN INDIVIDUAL CAGES AND WERE GIVEN A 3-CHOICE ACCESS TO UNFLAVOR ED ETHANOL (10 PERCENT SOLUTION), FLAVORED (SWEETENED AND SALTED) ETHANOL AND WATER. THE DAILY INTAKE OF THE FLAVORED ETHANOL SOLUTION WAS MUCH LOWER IN THE COLONY RATS THAN IN THE INDIVIDUALLY CAGED AND GROUPED RATS (13.5 VS 20.2 AND 24.1 ML DAILY); THE UNFLAVORED ETHANOL INTAKE WAS LOW IN ALL 3 GROUPS (4.3, 4.7 AND 2.7 ML, RESPECTIVELY) AND LOWEST IN THE GROUPED RATS. WHEN THE FLAVORED ETHANOL WAS REMOVED, ETHANOL INTAKE BECAME SIMILARLY LOW (6.6, 7.4 AND 4.0 ML) IN THE 3 GROUPS. IT IS SUGGESTED THAT TH E STIMULI OF THE COLONIAL SITUATION ACT TO DECREASE THE MAXIMIZED ETHANOL INTAKE.

22.
KULKOSKY-P-J; SICKEL-J-L; RILEY-A-L. TOTAL AVOIDANCE OF SACCHARIN CONSUMPTION BY RATS AFTER REPEATEDLY PAIRED INJECTIONS OF ETHANOL OR LIC L. . PHARMACOL. BIOCHEM. BEHAV., PHOENIX, NY, 13: 77-80, 1980 .

FEMALE LONG-EVANS RATS (7 PER GROUP) WITH LIMITED ACCESS TO WATER WERE GIVEN 20-MIN ACCESS TO A NOVEL 0.1 PERCENT SACCHARIN SOLUTION, FOLLOWED BY AN INTRAPERITONEAL INJECTION OF ETHANOL (2.0, 3.5 G PER KG OF BODY WEIGH T), LITHIUM CHLORIDE (1.8 MEQ/KG) OR WATER 15 MIN LATER. ON THE NEXT 3 DAYS (WATER-RECOVERY DAYS) RATS HAD 20-MIN ACCESS TO WATER, AND THE ENTIRE CONDITIONING-RECOVERY CYCLE WAS REPEATED TWICE. ON THE 2D EXPOSURE TO THE SACCHARIN SOLUTION ALL DRUG-INJECTE D RATS DRANK LESS SACCHARIN THAN DID WATER-INJECTED RATS (ALL P < .05). THIS INHIBITORY AFFECT INCREASED WITH THE ETHANOL DOSE AND TRIAL REPETITION. ONLY THE GROUP RECEIVING THE LOWEST ETHANOL DOSE DRANK SACCHARIN ON THE FINAL AVERSION TESTS (2 ML VS 1 4 ML CONSUMED BY THE WATER CONTROLS).

23.
Kulkosky-P-J. Blood ethanol and free-choice ethanol intake in rats and their progeny. . Pharmacol. Biochem. Behav., Phoenix, NY, 13: 449-4 52, 1980. .

Outbred male and female Charles River Wistar rats demonstrated large interindividual variations in nocturnal blood ethanol level (bel) during ad lib access to food, water and an ethanol solution. Mean individual bel ra nged from 0-109 mg/dl, grand mean = 25.1 mg/dl (5.5 mm). The bels of all rats correlated with free-choice ethanol intakes. However, females in the initial generation showed a significantly greater (p < .05) ethanol intake (female means, 10.5 vs male me ans, 8.2 g per kg per 24 hr) that was unaccompanied by significantly greater bel (female and male means = 30.6 and 19.6 mg/ dl.) Across 3 derived generations, offspring from matings of rats that had exhibited high bels showed significantly higher (p < .05) bels (mean = 32.8 mg/dl) than offspring of rats that had exhibited low bels (mean = 25.1 mg/ dl), but there was no significant difference across generations in ethanol intake (respective means = 8.4 and 8.1 g/ kg/24 hr). In the 4th generation, there were significant differences between high and low bel rats (respective means = 35 and 15 mg/dl) and ethanol intake ( respective means = 8.2 and 6.3 kg/24 hr).

24.
KULKOSKY-P-J. EFFECT OF ADDITION OF ETHANOL AND NACL ON SACCHARIN + GLUCOSE POLYDIPSIA. . PHARMACOL. BIOCHEM. BEHAV., PHOENIX, NY, 10: 277 -283, 1979. .

OUTBRED MALE WISTAR RATS (N = 90; 18 GROUPS) WERE GIVEN A CHOICE BETWEEN PLAIN WATER OR WATER SOLUTIONS CONTAINING 0.125 PERCENT SACCHARIN, 3 OR 9 PERCENT GLUCOSE AND 1.0 PERCENT SODIUM CHLORIDE, ALONE OR IN COMBINATIO NS, OR NO FLAVORING, TO WHICH ETHANOL WAS ADDED IN CONCENTRATIONS GRADUALLY INCREASING FROM 0.5 TO 15 PERCENT, 1 CONCENTRATION INCREMENT ON EACH OF THE 15 DAYS; CONTROL GROUPS HAD A CHOICE BETWEEN PLAIN AND FLAVORED WATER. IN THE NEXT STAGE, ETHANOL GROUP S WERE GIVEN A CHOICE BETWEEN THE FLAVORED FLUID WITH 2.5 PERCENT ETHANOL ADDED AND WATER FOR 5 DAYS. IN THE 3D STAGE, ALL GROUPS WERE GIVEN A CHOICE BETWEEN WATER AND UNFLAVORED ETHANOL SOLUTIONS, GRADED IN CONCENTRATION OVER ANOTHER 15-DAY PERIOD. FLAVO RING WITH GLUCOSE GREATLY AUGMENTED ETHANOL INTAKE. ETHANOL INTAKES OF THE SACCHARIN + 3. 0 PERCENT GLUCOSE + NACL + ETHANOL GROUP WERE HIGHEST, PEAKING AT 9. 0 G PER KG OF BODY WEIGHT PER DAY (AT 2 AND 2.5 PERCENT ETHANOL), AND THIS GROUP DISPLAYED THE H IGHEST BLOOD ETHANOL LEVELS (40 MG/DL AT MIDNIGHT AND 10.8 AT NOON ON THE 4TH DAY AFTER STARTING THE 2.5 PERCENT ETHANOL PROTOCOL). HOWEVER, THERE WAS NO EVIDENCE OF WITHDRAWAL SYNDROME OR OF INCREASED INTAKE OF UNFLAVORED ETHANOL BY GROUPS PREVIOUSLY REC EIVING FLAVORED ETHANOL. WHEN ETHANOL CONCENTRATIONS WERE ABOVE 3.5 PERCENT, ALL GROUPS DECREASED THEIR INTAKE BOTH IN TERMS OF SOLUTION VOLUME AND ABSOLUTE ETHANOL. THIS DECLINE OF INTAKE MAY REFLECT AN INCREASING AVERSION TO EITHER THE ORONASAL SENSORY OR MALAISE-PRODUCING PROPERTIES OF ETHANOL. IT IS SUGGESTED THAT THE RATE OF ETHANOL ELIMINATION MAY EFFECTIVELY LIMIT THE CAPACITY OF FREE- CHOICE INTAKE AND THAT SOME DEGREE OF FOOD OR WATER RESTRICTION MAY BE NECESSARY TO ACHIEVE A RAT MODEL OF ETHANOL ADDICTION.

25.
KULKOSKY-P-J; CORNELL-N-W. FREE-CHOICE ETHANOL INTAKE AND ETHANOL METABOLISM IN THE HAMSTER AND RAT. . PHARMACOL. BIOCHEM. BEHAV., PHOENIX , NY, 11: 439-444, 1979. .

THE RELATIONSHIP BETWEEN ETHANOL CONSUMPTION AND ETHANOL METABOLISM WAS STUDIED IN 22 MALE GOLDEN HAMSTERS AND 9 MALE WISTAR RATS; HAMSTERS DEMONSTRATED GREATER ETHANOL INTAKE AND PREFERENCE (ETHANOL SOLUTION/ TOTAL FL UID INTAKE THAN DID RATS (P < .05) WHEN GIVEN A CHOICE BETWEEN WATER AND 1-14 PERCENT ETHANOL. AS ETHANOL WAS GRADUALLY ADDED TO A SWEET SOLUTION (0.5-10 PERCENT, 10-20 PERCENT, 20-40 PERCENT AND 40-70 PERCENT), ETHANOL INTAKE BY HAMSTERS DID NOT CONSI STENTLY EXCEED ETHANOL METABOLIC CAPACITY FOR PROLONGED PERIODS. IN UNTREATED HAMSTERS AND RATS, ALCOHOL DEHYDROGENASE (ADH) ACTIVITIES AND ETHANOL METABOLIC RATES OF ISOLATED HEPATOCYTES WERE CORRELATED (R = .85, P < . 05). IN ETHANOL-TREATED HAMSTERS ADH DID NOT DIFFER FROM UNTREATED HAMSTERS, BUT WAS HIGHER THAN THAT OF UNTREATED RATS (P < .05). BLOOD ETHANOL ELIMINATION RATES AFTER INTRAPERITONEAL ADMINISTRATION OF 1.5 G OF ETHANOL PER KG OF BODY WEIGHT (10 PERCENT SOLUTION) WAS HIGHER IN HAMSTE RS THAN IN RATS (P < .05). IT IS SUGGESTED THAT ETHANOL METABOLISM PLAYS A LIMITING ROLE IN THE REGULATION OF MAXIMIZED FREE- SELECTION ETHANOL INTAKE BY RODENTS AND EXPLAINS THE ABSENCE OF CONTINUOUSLY ELEVATED BLOOD ETHANOL LEVELS AND ETHANOL WITHDRA WAL SYNDROME IN HAMSTERS DURING PERIODS OF COMPARATIVELY HIGH DAILY ETHANOL INTAKE.

26.
KULKOSKY-P-J. FREE-SELECTION ETHANOL INTAKE OF THE GOLDEN HAMSTER (MESOCRICETUS AURATUS) . PHYSIOL. PSYCHOL., AUSTIN, TX, 6: 505-509, 1978 . .

FEMALE GOLDEN HAMSTERS PREFERRED A 10 PERCENT ETHANOL SOLUTION IN A 0. 125 PERCENT SACCHARIN + 3 PERCENT GLUCOSE VEHICLE TO WATER IN SELECTION TESTS. THE GROUP RECEIVING SWEETENED ETHANOL CONSUMED 13.2 G PER KG OF BODY WEIGHT PER DAY COMPARED WITH 5.6 G/KG/DAY FOR THE WATER GROUP DURING THE 1ST 17 DAYS. REVERSAL OF VEHICLE TREATMENT FOR 10 DAYS DID NOT RESULT IN AN ABRUPT DECLINE OF ETHANOL INTAKE BY THE HAMSTERS WHICH HAD PREVIOUSLY RECEIVED SWEETENED ETHANOL, BUT A S UBSTANTIAL INCREASE IN ETHANOL INTAKE DID OCCUR IN A GROUP WHICH PREVIOUSLY RECEIVED UNSWEETENED ETHANOL. ALTHOUGH BLOOD ETHANOL LEVELS ATTAINED WERE HIGHER THAN PREVIOUSLY REPORTED FOR RATS IN SELECTION EXPERIMENTS, NO SYMPTOMS OF PHYSICAL DEPENDENCE ON ETHANOL WERE APPARENT IN A RUNWAY ACTIVITY TEST FOR WITHDRAWAL.

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