Central muscarinic activation elicits compulsive drinking behaviour in the rat

Injection of bethanechol into the lateral cerebral ventricle of the rat induces a marked increase in drinking, within 30 min from administration. The response is dose-related, maximal water intake (6.1 +/- 0.55 mL; mean +/- s.e.) occurring at 10 micrograms of bethanechol. Peripheral administration of the agonist (up to 3 mg kg-1 i.p.) fails to elicit drinking. Among several specific antagonists only antimuscarinic drugs produced a significant inhibition of the response, suggesting that the compulsive drinking behaviour in the rat is caused by activation of central muscarinic receptors. The drinking behaviour emerges as a reliable test to assess central muscarinic activity of both agonists and antagonists.     

Ethanol-induced inhibition of the drinking response to hypertonic saline in the rat

The effects of ethanol, in doses of 0.05, 0.1 and 0.2 ml/100 g, on the drinking responses of rats to subcutaneous injection of hypertonic saline (1 mEq/100 g) were examined. Rats were also studied for the effects of ethanol (0.1 ml/100 g) on drinking responses to intraperitoneal injection of dextran (20% w/v, 1.5 ml/100 g). After injection of hypertonic saline, rats given ethanol drank less than those administered water or isocalorific glucose. Ethanol inhibited the drinking responses to hypertonic saline dose-dependently with higher doses having a greater inhibitory effect. Ethanol administration had no effect on water consumption stimulated by intraperitoneal injection of dextran. It is concluded that administration of ethanol to rats has a dose-dependent inhibitory effect on thirst and fluid consumption stimulated by injection of hypertonic saline but is without effect on thirst and drinking stimulated by intraperitoneal injection of dextran.     

Effects of systemic and intracranial inhibition of angiotensin-converting enzyme on isoproterenol-induced drinking in the rat

We have investigated the effects of separate and combined s.c. and intracerebroventricular (i.c.v.) injections of captopril, an inhibitor of angiotensin I-converting enzyme, on isoproterenol-induced thirst. Whereas s.c. injections of captopril (0.5 mg/kg) increased drinking, combined s.c. and i.c.v. (20 μg) injections of captopril nearly abolished drinking to isoproterenol (0.1 mg/kg s.c.). This inhibition was not caused by general debility of the rats since the same treatment did not reduce drinking to 12 h water deprivation. Intracerebroventricular injection of 20 μg captopril alone also greatly reduced isoproterenol-induced drinking, perhaps because it leaked into the circulation; captopril i.c.v. also reduced the pressor response to i.v. injection of hog renin (0.1 Gold blattUnit) by about 65%. These results support the hypothesis that the renin-angiotensin system participates in the stimulation of drinking by isoproterenol and that the enhancement of drinking caused by inhibition of CE only in the circulation is the result of increased synthesis of angiotensin II in the brain.     

Endotoxin inhibition of distension-stimulated gastric acid secretion in rat: mediation by NO in the central nervous system.

1. The involvement of nitric oxide in the acute inhibitory effects of low doses of endotoxin, following intracerebroventricular (i.c.v.) or intravenous (i.v.) administration, on gastric acid secretion stimulated by distension or i.v. infusion of pentagastrin has been investigated in the continuously perfused stomach of the anaesthetized rat. 2. The i.c.v. administration of E. coli endotoxin (800 ng kg-1) abolished the acid secretory response induced by gastric distension (20 cm water intragastric pressure) within 30 min of administration. 3. By contrast, submaximal rates of acid secretion induced by i.v. infusion of pentagastrin (8 micrograms kg-1 h-1) were not inhibited by i.c.v. administration of endotoxin (800 ng kg-1). 4. Prior i.c.v. administration of the NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME, 800 micrograms kg-1) restored the acid secretory responses to distension in rats treated with endotoxin (i.c.v.). 5. Likewise, i.v. administration of endotoxin (5 micrograms kg-1) abolished the acid secretory response induced by gastric distension within 30 min of administration. Prior i.c.v. injection of L-NAME (800 micrograms kg-1) or its i.v. administration (10 mg kg-1) restored acid secretory responses in rats receiving i.v. endotoxin. 6. The reversal by L-NAME (i.v.) of the acid inhibitory effects of endotoxin (i.v.) was prevented by L-arginine (12 mg kg-1, i.c.v. or 100 mg kg-1, i.v.), but not by its enantiomer D-arginine. 7. The present results imply the existence of an acute response to endotoxin involving NO synthesis in the brain.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cholinergic stimulation of substantia nigra: effects on feeding,drinking and sexual behaviour in the male rat

Previous studies have shown that cholinergic stimulation of the substantia nigra increases food intake but not other activities. The present experiments were undertaken to determine whether or not activities other than feeding could be stimulated if conditions were appropriate. Microinjections of the cholinergic agonist carbachol (0.5 µg/0.5 µl each side) bilaterally into substantia nigra increased the consumption of dry spaghetti, and, in subsequent tests, changed sexual behaviour in male rats. Ejaculation, mount and intromission latencies were unaffected but intromission frequency (though not mount frequency) was reduced following cholinergic stimulation (experiment 1). In a second experiment, an increase in the consumption of 2.0% saccharin solution and lab chow was stimulated by intranigral carbachol while the intake of tap water, and locomotion, gnawing, grooming, rearing and sniffing were all unaffected. These data indicate that cholinergic stimulation of substantia nigra can affect activity for which there is a pre-existing tendency, regardless of its form. A possible role for nigral acetylcholine in the control of pars compacta dopamine containing neurones is discussed.     

Effect of domperidone on apomorphine inhibition of the copulatory response and exploratory behaviour in the female rat

The effects of domperidone, a peripheral dopamine receptor blocker which poorly crosses the blood-brain barrier, on copulatory and exploratory behaviour were studied in apomorphine (oestrogen + progesterone) treated ovariectomized rats. The dose of domperidone (1.0 mg/kg) which clearly prevented the inhibitory action of apomorphine on the lordotic response did not influence the effect of apomorphine in an exploratory test situation. This finding indicates that peripherally (intraperitoneally) administered domperidone influences dopaminergic mechanisms implicated in the copulatory behaviour of the female rat, but not dopaminergic mechanisms involved in exploratory behaviour. The possibility that domperidone reaches the brain region responsible for the lordotic behaviour, e.g. the hypothalamus, is discussed.     

Endotoxin inactivation by the humoral components in the tolerant rat serum

A rapid inactivation of endotoxin has shown to occur following its incubation in serum obtained from endotoxin-tolerant rats with the aid of the limulus amebocyte lysate (LAL) assay. The tolerant rat had large quantities of lipopolysaccharide inhibitor (LPSI) activity, which does not appear to be complement. Heating tolerant rat serum for 60 min at 56 degrees C or the addition of lead acetate to the tolerant serum both resulted in the loss of LPSI activity. This paper focuses on the most unique properties of LPSI, namely it's alteration of activity after heating or the addition of lead acetate, compared with those properties of inhibitors for endotoxin which have been previously demonstrated by a number of investigators.     

Drinking motives,drinking restraint and drinking behaviour among young adults

Motives to drink alcohol are widely thought to be the proximal cognitive factors involved in the decision to consume alcohol beverages. However it has also been argued that the ability to restrain drinking may be a more proximal predictor of drinking behaviour. The current study aimed to examine the relationships between drinking motives, drinking restraint and both alcohol consumption and alcohol-related problems in a sample of young adults. A sample of 221 young adults (aged 17–34 years) completed self-report measures assessing drinking behaviour, motives for drinking and drinking restraint. Multiple regression analyses revealed that coping, enhancement and social motives were related to alcohol consumption and alcohol-related problems, while Cognitive and Emotional Preoccupation with drinking was related to all criterion variables. Further, the relationship between coping motives and drinking behaviour was mediated by preoccupation with drinking. The results are discussed in light of the roles of drinking motives and drinking restraint in risky drinking among young people, and implications for prevention and early intervention are presented.     

Induction of drinking by insulin in the rat

Unanesthetized rats were injected i.v. either with commercial regular insulin, or the diluting fluid of the commercial insulin solution used, or with 0.9% NaCl, and placed in individual cages containing no food. Water intake was measured for 2 hr. Injection of the hyposmolar diluting fluid containing glycerol and phenol slightly, but significantly, enhanced the water intake. Insulin in doses from 0.05 to 43.0 U/kg induced an additional drinking response, while 0.02 U/kg had no effect. A linear log dose—response for insulin-induced drinking was obtained between 0.05 and 21.0 U/kg. Small doses of insulin, thus, undoubtly, enhance water intake. Insulin could play a minor role in body water homeostasis in mammals.     

Measurement of baseline drinking behaviour in problem-drinking probationers,drinking drivers,and normal drinkers

Total alcohol consumption, rate of ingestion, sip size, and drink preference were measured for 25 probationers, 15 convicted drinking drivers and 15 normal drinkers during 2½-hour baseline drinking sessions held in an experimental bar environment. Problem-drinking probationers were found to have a drinking profile similar to that of hospitalized alcoholics obtained in an earlier study (Williams & Brown, 1974). Although six drinking drivers displayed alcoholic-type drinking profiles, on most measures drinking drivers as a group fell between problem-drinking probationers and normal drinkers without being significantly different from either. Differences in subjects' drink preferences between this and the earlier study were discussed in terms of recent changes in drinking-driving legislation.     

Alcohol expectancies, drinking refusal self-efficacy and drinking behaviour in Asian and Australian students

The effects of alcohol expectancies (AE) and drinking refusal self-efficacy (DRSE) in predicting alcohol consumption in Caucasians has been well studied. However, the role of AE and DRSE in Asian students is still not well understood. This study reported on this using Caucasian (n=98) and Asian (n=92) student samples. Participants completed the Alcohol Use Disorder Identification Test (AUDIT) to measure their hazardous alcohol consumption, and the drinking expectancy profile (DEP) to assess their alcohol related expectancies and ability to resist drinking in certain situations. Results showed that Caucasians reported significantly higher confidence, higher sexual interest, and higher tension reduction expectancies than Asians. Conversely, Asians significantly expected cognitive enhancement and negative consequences more than Caucasians. Relative to Caucasians, the Asian sample also reported that they would be more able to refuse alcohol when under social pressure. Results from regression analyses showed that for the Caucasian sample, AE, DRSE and their interactions were significant predictors of alcohol consumption. For the Asian group, the only significant effect to emerge was that DRSE was negatively related to alcohol consumption. The clinical implications of the differential pattern of results between the samples are discussed in terms of self-efficacy and negative consequences of alcohol consumption, especially when dealing with university aged individuals.     

Developing a perspective on women's drinking behaviour

Women's drinking behaviour has recently emerged as an issue. Problem drinking per se has been researched, but the emphasis on gender is a relatively novel focus. In the present paper, recommendations are made for a theoretical framework to guide research. They are developed from discussion of previous perspectives, and the trend from ethical to medical to diversified theory is noted. Previous research on gender differences is discussed, as well as work directed specifically at women. The proposed framework recognises the likelihood of a common core of theory which would be supplemented by gender-specific aspects. The need for a multidisciplinary approach is also discussed, as is the logic of treating drinking behaviour on a continuum. Finally, a recommendation is made for studying drinking behaviour in a context of other indulgent/appetitive behaviours such as eating and smoking.     

Benzodiazepine mechanisms and drinking in the water-deprived rat

Benzodiazepines (diazepam, midazolam, flurazepam and chlordiazepoxide) produced a hyperdipsia in rats which were well-adapted to a daily 22 hr water-deprivation schedule. The hyperdipsia occurred as a result of extensions in the time-course of drinking without impairment in the efficiency of drinking (rate of water intake). At doses larger than those associated with hyperdipsia, the rate of water consumption was markedly impaired, so that any extension in the duration of drinking was offset by the impaired efficiency. As a result, a non-monotonic relationship between dose of benzodiazepine and volume of water intake could be generated. The convulsant benzodiazepine, Ro5-3663, produced a reduction in drinking, at sub-convulsant doses and without general motor interference. This hypodipsia was completely reversed by concurrent treatment with either diazepam or midazolam. The results are discussed in terms of possible behavioural and biochemical mechanisms which may underlie benzodiazepine-induced hyperdipsia.     

Kinetic behaviour of thallium in the rat

1. In acute experiments anesthetized rats were treated with a subthreshold dose of 204Tl+, given intravenously in order to study the elimination kinetics of Tl+. Thallium disappeared from whole blood by means of two different half-lives (5 and 196 min, respectively), whereas VDbeta amounted to 1400 ml. The same kinetic parameters were found after chronic exposure to toxic amounts of Tl+. 2. After chronic exposure to thallium (10 or 30 ppm in the drinking water), the distribution of thallium over various organs proved non-specific. However, a pronounced accumulation was found in the renal medulla. 3. In view of the importance of the renal route in the elimination of Tl+ from the body and also because of the established accumulation of the toxic metal in the kidney, the influence of potent diuretic agents like furosemide and ethacrynic acid on the excretion of Tl+ was studied. The enhanced excretion of water and ions (Na+, K+, Cl-) was accompanied by a significantly accelerated excretion of thallium ions. High doses of ethacrynic acid (25 mg/kg) proved particularly powerful in this respect. Between the enhanced excretion of thallium and potassium ions a significant correlation was obvious, thus supporting the well-known similarity in the behaviour of these ions. The marked increase in renal elimination of thallium upon intensive diuretic treatment may be useful in the management of thallotoxicosis.     

Endotoxin inhibition of dexamethasone induction of tryptophan oxygenase in suspension culture of isolated rat parenchymal cells: Involvement of the hepatic nonparenchymal cell fraction

The effect of endotoxin on the induction of tryptophan oxygenase activity by dexamethasone has been studied in suspension cultures of isolated rat hepatic parenchymal cells incubated alone or mixed with hepatic nonparenchymal cells. Hepatic cellular fractions were isolated from untreated rats and from animals injected 2 hr prior to killing with 2 mg/kg of endotoxin. Endotoxin (400 μg/ml) added to suspensions of parenchymal cells from untreated animals did not decrease the induction of tryptophan oxygenase by dexamethasone. Endotoxin addition to cell suspension containing parenchymal and nonparenchymal cells from untreated rats caused a significant diminution in the induction of enzyme activity elicited by 0.1 μM, but not by 20 μM, dexamethasone. The nonparenchymal cell fraction from untreated animals had no effect on enzyme induction in the absence of added endotoxin. However, nonparenchymal cells isolated from rats pretreated in vivo with endotoxin diminished the induction of tryptophan oxygenase activity elicited by 0.1 and 20 μM dexamethasone even in the absence of added endotoxin. The inhibitory effect of nonparenchymal cells from endotoxin-pretreated rats was related to cell concentration and was accentuated by the in vitro addition of endotoxin. Parenchymal cells from the endotoxin-pretreated animals had an altered sensitivity to dexamethasone. The ec₅₀ concentration for dexamethasone induction of tryptophan oxygenase was 40 and 500 μm for parenchymal cells from untreated and endotoxin-pretreated animals respectively. Parenchymal cells from the pretreated animals were more sensitive to the inhibitory effect of the nonparenchymal cells from the pretreated animals. These results are interpreted as indicating that endotoxin does not directly antagonize the induction of tryptophan oxygenase. The results suggest that this inhibition of tryptophan oxygenase induction is a mediated event involving an interaction of endotoxin with cellular constituents of the hepatic nonparenchymal cell fraction.     

A cross-cultural application of a drinking behaviour questionnaire

A British Questionnaire for Drinking Behaviour (HDBQ) measuring the severity of alcoholism was applied cross-culturally to 96 Arab-Muslim alcoholics while receiving treatment in Kuwait Psychiatric hospital. Though HDBQ proved valid in differentiating Arab alcoholics drinking categories, it gave significantly lower scores for the Arab sample when compared to scores of a British sample. Statistical analysis of the responses of various categories showed that Arab patients tended to respond in absolute negatives significantly more than the British sample did. Cultural factors underlying this tendency were discussed. Suggestions are offered for improvements of this and similar diagnostic instruments to make them more usable transculturally.     

Centrally-administered opioid selective agonists inhibit drinking in the rat

The effects of intracerebroventricular injection of mu (morphine), kappa (dynorphin-(1-13), ethylketocyclazocine, and U50,488H), and delta ([D-Pen2, D-Pen5]enkephalin) opioid agonists on water intake of 14 hr water deprived rats was studied. All agonists caused a dose related decrease in time spent drinking, with a rank order potency of dynorphin-(1-13) greater than morphine greater than ethylketocyclazocine greater than [D-Pen2, D-Pen5]enkephalin = U50, 488H. With the exception of morphine, all of the compounds increased the latency to begin drinking, but only at the highest doses tested. The rank order potency for this endpoint was dynorphin-(1-13) = ethylketocyclazocine greater than [D-Pen2, D-Pen5]enkephalin greater than U50, 488H. The potent inhibition of drinking following centrally-given dynorphin-(1-13), at doses that did not affect the latency to begin drinking, supports a role for endogenous dynorphin in the homeostatic control of water balance. This function may not be primarily mediated through activation of a kappa opioid receptor since dynorphin-(1-13) was 80-230 times more potent than the selective kappa agonist, U50,488H or ethylketocyclazocine.     

Evidence that nitric oxide modulates drinking behaviour.

The involvement of the L-arginine-nitric oxide (NO) pathway in brain, in the regulation of drinking behaviour, has been evaluated by injecting L-arginine and N omega-nitro-L-arginine methyl ester (L-NAME) into the lateral cerebral ventricle (i.c.v.). L-Arginine (5 and 10 micrograms/rat), but not D-arginine, was antidipsogenic when administered to 24 hr water-deprived rats but did not change the intake of water in normally hydrated rats. However, L-NAME (5 and 10 micrograms/rat) did antagonize the effect of L-arginine in water-deprived animals but, by itself, did not increase thirst. L-Arginine (100 ng), when injected into the preoptic area significantly reduced water deprivation-induced drinking. The same dose was unaffective when given intraventricularly. Finally, L-arginine (5 and 10 micrograms/rat, i.c.v.) inhibited drinking induced by intraventricular injection of angiotensin II (250 ng/rat). The effect was dose-dependent. The results indicate that: (1) NO acts as an inhibitory mechanism when thirst is stimulated by water deprivation or by angiotensin II; (2) the preoptic area might be one of the central sites of antidipsogenic action of NO and (3) nitric oxide synthase might be inhibited during water deprivation.