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The role of brain catalase in the mediation of ethanol's effects on motor activity was investigated. Male Long-Evans rats were pretreated with i.p. injections of the catalase inhibitor, 3-amino-1,2,4-triarole (AT) (1 g/kg) or saline (S). Four hours later, animals in each group received i.p. injections of one of two doses of ethanol (ETOH) [1.0 g/kg (E1) or 2.0 g/kg (E2)] or one of two volumes of distilled water (W1 or W2). Ten minutes alter the administration of these agents, animals were placed in open-field chambers and motor activity was recorded during a 10-min testing period. Results indicated that the motor depression produced by 2.0 g/kg of ETOH was significantly attenuated in AT pretreated rats (group AT-E2). AT pretreatment, however, had no effect on motor activii for subjects injected with 1.0 g/kg ethanol or water. Total brain catalase activity in AT-pretreated animals was 15% of control animals. No differences in blood ethanol levels were obsewed between AT- and S-pretreated animals. An interaction between ethanol and AT at the level of the central nervous system is suggested. The results of the present study suggest that brain catalase activity may be involved in ethanol's effects. They also provide further support for the notion that acetaldehyde may be produced directly in the brain via catalase and that it may be a factor mediating some of ethanol's central effects. [ABSTRACT FROM AUTHOR]

Introduction: Several studies investigating the oral health status of children living in Ukraine after the Chernobyl catastrophe revealed an increase of caries in children residing in radionucleotide-contaminated areas., Purpose: (1) To compare prevalence of dental caries in contaminated and noncontaminated towns; and (2) to determine if there is a difference between dental behaviors and attitudes of children residing in contaminated and noncontaminated areas that may have contributed to differences in caries prevalence., Methods: Children aged 13-14 were randomly selected in two towns of approximately the same population size (33 000): Ovruch (n = 119) from a contaminated area and Mirgorod (n = 100) from a noncontaminated area. Data on behaviors and attitudes were collected via a self-administered questionnaire having six domains: (i) family background; (ii) dental anxiety; (iii) dental utilization; (iv) oral hygiene; (v) use of fluoride toothpaste; and (vi) sugar consumption. Oral examinations included information on carious lesions, restorations, missing teeth, and soft tissue abnormalities. Caries prevalence was compared using a t-test. Regression analysis was conducted to determine the independent contribution of oral hygiene behaviors and dental utilization., Results: There was a significant difference in caries prevalence in the contaminated town (mean DMFT = 9.1 +/- 3.5) versus the noncontaminated town (mean DMFT = 5.7 +/- 1.4; P < 0.000). Oral hygiene practices, age, and utilization of dental services were not found to be associated with differences in DMFT score between the two communities., Conclusion: There was a significantly higher caries prevalence in a radiation-contaminated town compared to a noncontaminated town of Ukraine. The difference was not explained by differences in oral health knowledge, attitudes or behaviors., (Copyright Blackwell Munksgaard, 2004)

Cyanamide, an aldehyde dehydrogenase inhibitor, has been shown to suppress voluntary ethanol consumption in animals. Studies were carried out to compare the effect of cyanamide on ethanol, saccharin-quinine and water intake in a restricted (10 min) access and in a free-choice nonrestricted access paradigm. An immediate and constant increase in fluid consumption was observed in the restricted access schedule paradigm independent of the fluid tested as cyanamide affected the consumption of all fluids including water. In the nonrestricted access study, cyanamide significantly increased total fluid intake. However, while saccharin-quinine-drinking animals treated with cyanamide demonstrated no change in intake preference, ethanol consumption was suppressed with a concomitant decrease in preference for ethanol. The present findings suggested that cyanamide may possess at least two, paradigm-specific, independent properties. It may enhance the consumption of fluid in general; however, it may also have a specific effect on ethanol intake when animals have continuous ethanol availability.

Unlabelled: The procedures and findings of a previous study were replicated. Sixty-one men and 35 women were randomized to one of three treatments: Manual: three sessions of instructions in use of a manual describing a step-by-step method for attaining abstinence or moderate drinking., Guidelines: three sessions of advice using a pamphlet summarizing the contents of the manual. Therapist: application of the step-by-step method in an indefinite number of sessions. At 3-month follow-up, the number of Moderate drinkers was again significantly higher among women than men in the GUIDELINES (77% versus 24%) and Manual conditions (75% versus 33%), but not in the Therapist condition (50% versus 53%). Again, at 1-year more women than men were Moderate drinkers in all conditions (69% versus 31% overall). Changes from baseline in GGT, MCV, and the Digit Symbol Test corroborated the clients' reports of drinking. In this study the more experienced therapists had significantly lower rates of client dropout than the less experienced. Clinical and research implications of the findings are discussed.

The effects of pimozide were examined in a runway paradigm using food reward. Rats received one of three doses of pimozide, vehicle or Ringer's prior to testing. Two additional groups received pimozide or vehicle after the test trial in the home cage. An extinction group received no food in the goal box on test days. Several components of running behavior were assessed as was food consumed in the goal box. Effects of pimozide on general locomotor activity were assessed in the open-field following the runway phase. Results of the runway indicated that pimozide-treated rats differed from the extinction group in latencies to leave the start box and enter the goal box. Pimozide-treated rats consumed less saccharin-flavored food than controls. The post-treatment pimozide group showed a reduction in saccharin-food intake suggesting a conditioned taste aversion. Thus, the reduction observed in the pretreated pimozide group may be due to some unconditioned aversion induced by the drug. Open-field revealed that pimozide resulted in lower activity than controls. This study indicates that the effects of pimozide on food reinforcement are not similar to the effects seen in extinction. These data are consistent with the hypothesis that the effects of pimozide, in this paradigm, constitute an interference with motor responses as opposed to an attenuation of reward properties of the stimuli.

Previously, in an investigation of morphine-conditioned taste aversion (CTA), we found that limited preexposure to a low, nonaversive (non-CTA-inducing) dose of morphine (2.5 mg/kg) was as effective as preexposure to a higher, CTA-inducing dose (15 mg/kg) in blocking the formation of a subsequent morphine CTA. In the present study, we examined the capacity of this low, 2.5-mg/kg morphine dose to maintain a CTA initially induced by the 15-mg/kg dose. A standard CTA procedure was used. Results indicated that rats given three initial taste-drug pairings with 15 mg/kg morphine followed on subsequent pairing days by treatment with the low, non-CTA-inducing, 2.5-mg/kg dose continued to exhibit a strong CTA over 8 pairing days. A similar pattern was observed for animals continuing to receive taste-drug pairings with the 15-mg/kg dose. Animals receiving only one taste-drug pairing with the 15-mg/kg dose, followed on subsequent pairing days by 2.5-mg/kg conditioning, failed to show such a pattern of CTA. An intermediate CTA pattern was seen with animals conditioned with 15, 10, 5, and repeated 2.5-mg/kg doses over consecutive pairing days. These data suggest that exposure to a low dose of morphine, with no apparent CTA-inducing properties, is sufficient to maintain a previously established morphine taste aversion. Potential implications for understanding the apparent discriminative complexity of morphine's motivational properties are discussed.

The role of brain aldehyde dehydrogenase (ALDH) and acetaldehyde in mediating ethanol-induced locomotor activity was investigated using several enzyme inhibitors. Cyanamide, an ALDH inhibitor elevates blood acetaldehyde levels in the presence of ethanol. Concurrent administration with 4-methylpyrazole, an alcohol dehydrogenase inhibitor, prevents peripheral accumulation of acetaldehyde by cyanamide. Two hr prior to testing locomotor activity in open field boxes, 111 male Long Evans rats were pretreated with i.p. injections of saline (S+S), 4-methylpyrazole (4MP+S), cyanamide (S+C) or 4-methylpyrazole + cyanamide (4MP+C). Subjects then received i.p. injections of one of three doses of ethanol (0.4, 0.8 or 1.2 gm/kg) or saline vehicle one minute prior to testing in the open field and locomotor activity was recorded for a 10 min period. Locomotor activity of animals pretreated with cyanamide (S+C and 4MP+C) was significantly depressed compared to groups S+S and 4MP+S particularly at the two lower doses tested. These effects cannot be attributed to elevated blood acetaldehyde levels since pretreatment with 4MP+C prevented peripheral accumulation of acetaldehyde. A characteristic common to both cyanamide-treated groups was the inhibition of brain ALDH. It is therefore suggested that brain ALDH may play a role in the mediation of locomotor effects produced by ethanol. It is conceivable that ALDH plays this role by regulating the levels of acetaldehyde in brain.

In an attempt to examine the potential aversive properties of the neuroleptic pimozide, a conventional conditioned taste aversion (CTA) paradigm was employed. Rats were either pretreated with pimozide (1.0 mg/kg) before the presentation of a familiar or novel saccharin-flavored solution or tap water or received injections of pimozide after the presentation of a novel saccharin solution. Following this procedure, rats were given a two bottle choice test under drug-free conditions. All pretreated pimozide groups demonstrated a significant unconditioned reduction in fluid intake relative to the vehicle control group. These pimozide groups having different drinking histories did not differ from one another. Although pimozide did not induce a CTA in rats post-treated with this neuroleptic, overall this group drank significantly less saccharin than the control group. Furthermore, on the two bottle choice test, rats which received contingent exposure to pimozide and saccharin (pre and post conditions), did not demonstrate a preference for the saccharin solution. These results suggest that the reduction in fluid intake observed in the pretreated pimozide groups may be due to some unconditioned aversive state induced by the drug. These data indicate that the mechanisms involved in the reduction of fluid intake induced by pimozide may be unrelated to a manipulation of the reinforcing properties of the appetitive stimulus.

The role of peripherally and centrally acting acetaldehyde in ethanol-induced conditioned taste aversion (CTA) was investigated using various enzyme manipulations. Cyanamide, an aldehyde dehydrogenase inhibitor (ALDH) elevates blood acetaldehyde levels in the presence of ethanol. Concurrent administration with 4-methylpyrazole (4MP), an alcohol dehydrogenase inhibitor, prevents peripheral accumulation of acetaldehyde by cyanamide. Under both treatment conditions brain and liver ALDH activity is inhibited. Water-deprived rats were pretreated 4 hr prior to fluid presentation with intraperitoneal injections of saline (S+S), 4-methylpyrazole (4MP+S), cyanamide (S+C), or 4-methylpyrazole + cyanamide (4MP+C). Subsequently, animals were presented with a novel saccharin solution followed immediately by intraperitoneal injection of one of three doses of ethanol (0.4, 0.8, or 1.2 g/kg) or saline vehicle on four occasions. Results suggested that animals pretreated with cyanamide (groups S+C and 4MP+C) drank significantly less saccharin after conditioning with a subthreshold dose of ethanol (0.4 g/kg) in comparison to groups S+S and 4MP+S. Moreover, at the conditioning dose of 1.2 g/kg, cyanamide-treated animals demonstrated an attenuation of CTA compared to the other two groups. These effects cannot be attributed to elevated blood acetaldehyde levels since pretreatment with 4MP+C prevented peripheral acetaldehyde accumulation. A characteristic common to both cyanamide-treated groups was the inhibition of brain ALDH. It is therefore suggested that brain ALDH may play a role in the mediation of ethanol-induced CTAs. It is conceivable that ALDH plays this role by regulating the levels of acetaldehyde in brain.

Unlabelled: Problem drinkers (52 males, 38 females) recruited through advertisements were randomly assigned to one of three treatments:, Guidelines: three sessions of advice using a pamphlet outlining basic steps for achieving abstinence or moderate drinking. Manual: three sessions of instruction in the use of a 'self-help' manual presenting a step-by-step approach for attaining abstinence or moderate drinking. Therapist: six or more sessions of instruction in the methods outlined in the 'self-help' manual. At 3, 6 and 12 months follow-up, no significant differences were found among the groups in reduction of heavy drinking days (i.e. days when consumption exceeded four drinks, each containing 13.6 g/ethanol). Overall, the number of heavy days were reduced from an average of 43 at intake, to 20 over the 1-year follow-up period. Females, however, had significantly greater reductions than males (75% versus 35%). Three months after treatment the rate of successful moderate drinkers was significantly higher for females than males in the GUIDELINES (60% versus 33%) and the Manual condition (63% versus 18%), but not in the Therapist condition (25% versus 35%). At 1-year follow-up, females were more successful than males in all conditions. Mean changes in GGT and MCV levels lended support to the change in drinking status (from heavy drinker at intake to moderate drinker at follow-up), based on clients' self-reports.

Laboratory rats in a 24 hr free choice paradigm consume ethanol in a series of discrete drinking bouts. However, little research has been directed at establishing whether these individual bouts were pharmacologically relevant to animals. The present study was designed to investigate the pharmacological efficacy of a simulated ethanol drinking bout and the possible role of acetaldehyde (ACH) and its metabolizing enzymes in mediating these effects using various enzyme manipulations. Following an ethanol screening procedure (2% to 10%, free choice) to establish a drinking baseline, animals were deprived of ethanol for a two week period. Using a limited access procedure, animals were then presented with a 10% ethanol solution for a 10 min period each day for 10 days. On Days 11-15, 4 hr prior to ethanol presentation, animals were divided into four groups and received i.p. injections of either saline (S), 4-methylpyrazole (4MP), cyanamide (C) or 4-methylpyrazole + cyanamide (4MP + C). This latter treatment condition has been shown to prevent the accumulation of ACH in the periphery by cyanamide. On Day 12, 10 min after the drinking session, animals were placed in open field chambers and locomotor activity was recorded for 5 min. Results indicated that animals pretreated with cyanamide (groups S + C and 4MP + C) consumed significantly more ethanol across the 5 test days than groups S + S and 4MP + S. Locomotor activity was significantly depressed for animals pretreated with cyanamide alone (C + S), although drinking levels were comparable to all other groups on Day 12. Together, these data demonstrate that a stimulated drinking bout is a pharmacologically meaningful event since it can be altered by manipulating acetaldehyde-metabolizing enzymes.(ABSTRACT TRUNCATED AT 250 WORDS)

Interpretation of the finding that positive-reinforcing drugs such as morphine also possess possible aversive properties, as revealed by their ability to induce a conditioned taste aversion (CTA), remains problematic. This issue was addressed in the present study using the drug preexposure CTA paradigm. Water-deprived rats were given noncontingent preexposure to one of three doses of morphine (2.5, 5.0, or 15.0 mg/kg) or drug vehicle. Subsequently, animals in each of these preexposure groups were presented with a novel 0.1% saccharin-flavored solution followed immediately by injection with one of the same three morphine doses or drug vehicle. This procedure was repeated at 5-day intervals until six saccharin presentations had been performed. Results indicated that while the three morphine doses were differentially potent as taste aversion-conditioning agents, they were equipotent as preexposure agents serving to disrupt CTA. These data suggest that preexposure to morphine's predominantly positive-reinforcing (and non-CTA-inducing) properties is sufficient for preexposure disruption of subsequent morphine CTA. A second experiment indicated that the minimal effective preexposure dose is between 0.3 and 1.25 mg/kg of morphine. It is suggested that an important commonality may exist between the discriminative stimulus properties of morphine as a CTA-inducing agent and as a positive reinforcer.