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PubMed1983

Experiments on the neuropsychology of thirst.

We report the results of a series of experiments whose main objectives are: (a) the identification of neural receptors for thirst; and (b) other neural structures of critical importance for thirst and drinking behavior. We have used results from hypertonic challenges during acute unit and multiple-unit recording experiments to identify responsive brain areas for behavioral study in chronic experiments. Results include the following. Single cells in the lateral preoptic area (LPOA) responded to injections of hypertonic saline into the carotid artery in a dose-related manner. Multiple unit activity (MUA) reactions were invariably facilitatory to challenge, and were much greater in the LPOA than in the medial preoptic area (MPOA). In unit and MUA recording we found extremely osmosensitive sites in the dorsal midbrain. Comparing the effects of NaCl vs sucrose as challenges via the intracarotid artery we found that LPOA MUA responses to sucrose were at least as strong and latencies as short as those to NaCl. These results support osmoreceptor theory, as revised by Epstein and his co-workers, and they are opposed to Andersson's sodium receptor theory. Hypertonic NaCl and sucrose solutions (but not artificial CSF controls) injected into the lateral ventricle were effective in producing strong MUA reactions, which typically were inhibition followed by facilitation. These and other findings support the following conclusions. (a) The LPOA appears to be a vital part of the neural mechanism for thirst and it is a probable site of osmoreceptors. (b) In addition, the LPOA seems to be a receiving area connected with putative periventricular neural receptors. (c) Intraventricular (i.v.t.) angiotensin II seems to be a much stronger dipsogen than hypertonic NaCl i.v.t., which in higher concentrations elicited stereotyped running.

Angiotensin II↗
PubMed2001

Sensitivity and specificity of carbohydrate-deficient transferrin in drinking experiments and different patients.

Information provided by patients about the amounts of alcohol they drink may often be too subjective and therefore unreliable. Because of the possible serious consequences of interactions between alcohol and medication, reliable laboratory test markers for alcohol consumption are needed. Carbohydrate-deficient transferrin (CDT) is at present the best available objective measure of drinking behavior. During a withdrawal trial, 92 alcohol-dependent patients who had been admitted to a hospital in an ethanol-intoxicated state were monitored over the following 28 days by using the percent carbohydrate-deficient transferrin (%CDT of total transferrin) (%CDT) method. At the time of admission, 63% showed elevated %CDT levels. After a subsequent period of abstinence, a decrease in %CDT levels was apparent in four different groups of patients, whereas in two groups, comprising the greatest number of patients, normal %CDT levels were evident after 14 days of abstinence. In patients whose CDT levels were very high at study initiation, it took at least 21 to 28 days--and sometimes longer--for CDT to decrease to the radioimmunoassay (RIA) %CDT test cutoff point of 2.5. In a further study of 56 male alcohol-dependent patients, we measured liver enzyme concentrations, mean corpuscular volume (MCV), and four CDT variants on the first day of evidence of withdrawal syndrome. We found a significant correlation between results on the Munich Alcoholism Test (MALT) and MCV levels; among gamma-glutamyltransferase (GGT), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) levels; and among all four CDT variants. A cluster analysis yielded three clusters: (1) GGT, AST, and ALT levels; (2) MCV levels and MALT results; and (3) all CDT measurement variants. We conclude that these three clusters measure different detriments to the patient and that all available CDT variants are commensurate.

Alcohol Drinking↗
PubMed1993

Reduction of spontaneous alcohol drinking and physical withdrawal by levemopamil, a novel Ca2+ channel antagonist, in rats.

Neuronal Ca2+ channels have been shown to be involved in both alcohol drinking behavior in rats and nonhuman primates and in the manifestation of alcohol withdrawal symptoms in rodents. Experiments were performed to determine the effect of a single injection of levemopamil, a novel Ca2+ channel antagonist with antiserotonergic [5-hydroxytryptamine2 (5-HT2)] properties, on alcohol preference and alcohol withdrawal symptoms in alcohol-preferring (P) and Wistar rats, respectively. P rats were individually housed and provided free access to food, water, and a solution of 10% (v/v) ethanol. Ethanol, food, and water intakes were measured daily. After establishing a stable baseline, P rats were injected with levemopamil (0, 3.3, 10, 15, and 20 mg/kg) and their food, water, and alcohol intakes measured 24 h later. In a separate experiment, the ability of acute and chronic (12 consecutive days) administrations of levemopamil to suppress alcohol withdrawal symptoms in chronically alcohol-treated rats was studied. In addition, the effects of levemopamil on the level of monoamines in different areas of the brain, as well as its action in alcohol metabolism, were examined. Our findings showed that a single administration of levemopamil (10, 15, and 20 mg/kg) significantly and dose-dependently attenuated alcohol intake and increased water intake in P rats. Both acute and chronic treatment with levemopamil reduced the alcohol withdrawal symptoms, overall seizure scores, and proportion of rats seizing. A single injection of levemopamil produced a clear, but not significant, trend to increase the 5-HT turnover rate in certain brain areas. This drug did not influence the pharmacokinetics of alcohol.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcohol Drinking↗
PubMed2002

The decreased cellular expression of neuropeptide Y protein in rat brain structures during ethanol withdrawal after chronic ethanol exposure.

BACKGROUND: Neuropeptide Y (NPY) has been implicated in the alcohol-drinking behaviors of rodents. This study investigated the possible involvement of NPY in the neuroadaptational mechanisms to chronic ethanol exposure and its withdrawal. METHODS: Male Sprague-Dawley rats were treated either with Lieber-DeCarli ethanol diet or control diet for 15 days, and ethanol-fed rats were withdrawn for 0 and 24 hr. The protein expression of NPY was determined in cortical, hippocampal, amygdaloid, striatal, and hypothalamic structures by using the gold-immunolabeling histochemical procedure. RESULTS: It was found that ethanol withdrawal, but not ethanol treatment, produced significant reductions in NPY protein levels in (1) layers IV and V of the frontal and parietal cortex, (2) layer II of the piriform cortex, (3) the central and medial nuclei of the amygdala, and (4) the paraventricular nucleus of the hypothalamus in rat brain. Chronic ethanol exposure and its withdrawal had no effect on the NPY protein levels in layers II, III, and VI of the frontal and parietal cortex or cingulate gyrus, in hippocampal (CA1, CA2, CA3, and dentate gyrus) and striatal (caudate putamen and globus pallidus) structures, or in the ventro-medial hypothalamus and basolateral amygdala. However, chronic ethanol exposure and its withdrawal produced significant reductions in NPY protein levels in the arcuate nucleus of the hypothalamus and in layers IV and V of the cingulate gyrus. CONCLUSIONS: These results suggest that the decreased protein levels of NPY in the central and medial nuclei of the amygdala, as well as in the cortical and hypothalamic structures, during ethanol withdrawal may play an important role in the neuromechanisms of some ethanol withdrawal symptoms.

Alcohol Drinking↗
PubMed2003

Salsolinol produces reinforcing effects in the nucleus accumbens shell of alcohol-preferring (P) rats.

BACKGROUND: The formation of salsolinol (SAL) has been hypothesized to be a factor contributing to alcoholism and alcohol abuse. If SAL is formed under chronic alcohol-drinking conditions, then it may contribute to alcohol addiction by being rewarding itself. Because SAL can be formed by the nonenzymatic condensation of acetaldehyde with dopamine, the reinforcing effects of SAL were tested in the nucleus accumbens shell, a dopamine-rich site considered to be involved in regulating alcohol-drinking behavior. METHODS: The intracranial self-administration technique was used to test the reinforcing properties of SAL. Adult, female alcohol-preferring (P) rats were stereotaxically implanted with guide cannulae aimed at the nucleus accumbens shell. After 7 to 10 days to allow recovery from surgery, P rats were attached to the electrolytic microinfusion transducer system, placed in two-lever experimental chambers, and allowed to respond for the self-infusion of 100 nl of modified artificial cerebrospinal fluid (aCSF) or 0.03, 0.3, 3.0, or 12.5 microM SAL (3-1250 fmol/100 nl). Sessions were 4 hr in duration and were conducted in the dark cycle every 48 hr. The effects of coinfusing 10 to 400 microM sulpiride (given in sessions 5 and 6 after four acquisition sessions) on the intracranial self-administration of 3.0 microM SAL were tested in a separate experiment. RESULTS: P rats given 0.3 to 12.5 microM SAL received significantly more infusions per session than did the group given aCSF alone (e.g., 50 infusions for 3.0 microM SAL versus 10 or fewer infusions for the aCSF group) and responded significantly more on the active than inactive lever. Coinfusion of 100 or 400 microM sulpiride reduced the responding on the active lever (80-100 responses/session without sulpiride) to levels observed for the inactive lever (fewer than 10 responses/session with sulpiride). This effect was reversible because giving SAL alone in session 7 reinstated responding on the active lever. CONCLUSIONS: SAL is reinforcing in the nucleus accumbens shell of P rats at concentrations that are pharmacologically possible, and these reinforcing actions are mediated in part by D2/D3-like receptors.

Alcohol Drinking↗
PubMed2005

Ethanol consumption increases rat stress hormones and adrenomedullary gene expression.

Numerous reports document altered drinking behavior following acute stressors but few describe physiological responses to acute stress of chronic ethanol consuming subjects. We tested rats' responses to 120-min foot restraint immobilization (Immo) after 1 week of liquid diet containing 5% wt/vol ethanol (ethanol-fed). Controls consumed isocaloric liquid diet ad libitum (adlib-fed) or in amounts equal to that of ethanol-fed subjects on the previous day (pair-fed). Each rat was implanted with a tail artery cannula on day 7 to allow remote blood collection before and during Immo on day 8. Plasma epinephrine (Epi); norepinephrine (NE); corticosterone (Cort); prolactin (PRL); adrenomedullary gene expression of catecholamine biosynthetic enzymes tyrosine hydroxylase (TH), dopamine beta-hydroxylase (DBH), and phenylethanolamine-N-methyl transferase (PNMT); and TH protein levels were measured. Ethanol-fed rats had two to threefold higher basal plasma Epi and NE and tended to have increased Cort compared to adlib-fed or pair-fed rats. Immo increased Epi and NE in ethanol-fed rats more than twofold above those observed in controls, and also increased Cort more in ethanol-fed than in control rats. PRL was marginally affected. Ethanol potentiated the normal immobilization-induced increase in adrenomedullary TH, DBH, and PNMT messenger RNA (mRNA). TH protein increased only in ethanol-fed rats. Increased plasma catecholamine levels, adrenomedullary gene expression, and TH protein concentration in nonimmobilized ethanol-fed rats strongly suggest that ethanol consumption was itself a stressor, which potentiated the subsequent response to acute Immo. Moreover, the observed interaction of ethanol and stress on plasma catecholamine levels illustrates the importance of minimizing additional stressful stimuli when investigating ethanol's physiological effects.

Adrenal Medulla↗
PubMed1992

Early development of the human area postrema and subfornical organ.

The first appearance and early development of two circumventricular organs, the area postrema (AP) and the subfornical organ (SFO), were investigated in human embryos and fetuses from the 4th to the 40th gestational weeks (GW). The AP appears very early in development, during the GW 10; its high vascularization can be seen from GW14, and differentiated neurons are observed from GW 16. The SFO is characterized by a late onset of development. It can first be distinguished at GW 17, but it does not attain cytological differentiation until the last weeks of gestation. It is suggested that the AP has important functions during fetal life, which are related to normal fetal weight and growth; in contrast the SFO, which is connected with drinking behavior and salt/water balance, seems to play a less essential role in early fetal life.

Body Weight↗
PubMed2005

Water deprivation increases the expression of neuronal nitric oxide synthase (nNOS) but not orexin-A in the lateral hypothalamic area of the rat.

The discovery that the lateral hypothalamic area (LHA) might be important in modulating drinking behavior and fluid balance has led to numerous studies aimed at identifying the key neurotransmitters/neuromodulators and pathways involved. While past studies have demonstrated the presence of neuronal nitric oxide synthase (nNOS) within the LHA, its role in the regulation of fluid homeostasis is not known. In light of this, and the mounting evidence suggesting a role for nitric oxide in osmotic regulation within the hypothalamus, this study sought to determine the effects of 24- and 72-hours of water deprivation on nNOS protein expression within the LHA of the rat with immunohistochemistry. In euhydrated control animals we observed nNOS-like immunoreactivity throughout all levels of the LHA. Following 24 hours of dehydration the number of nNOS-like immunopositive neurons was significantly increased in the rostral but not the caudal regions of LHA. Seventy-two hours of water deprivation lead to further increases in nNOS-like immunoreactivity at different levels of the LHA. Interestingly, however, we observed increased nNOS-like immunoreactivity in the caudal regions of the LHA that was not evident after 24 hours of water deprivation. Double-labeling immunofluorescence histochemistry revealed that the nNOS-like immunoreactive neurons were not colocalized with the orexin-A-containing neurons. These results suggest that an osmotic challenge leads to an upregulation of nNOS immunoreactivity within discrete areas of the LHA. This altered neurochemistry within the LHA further highlights the potential importance of nitric oxide and the LHA in central regulation of fluid homeostasis.

Animals↗
PubMed1978

Competitive social strategies in groups of deprived and experienced rhesus monkeys.

Behavior during competition for water was observed in 2 social groups of young rhesus monkeys (3 females, 3 males in each). Monkeys in one group were socially deprived and those in the other were socially experienced (raised with mother and agemates). Social status, based on dyadic recording of displacements at the water bottle, was predictive of a number of measures related to water consumption and social orientation in both groups, but this measure was less reliable and predictive for the experienced group than for the deprived groups, but this measure was less reliable and predictive for the experienced group than for the deprived group. A major reason for the comparatively low predictive value and reliability of status among experienced monkeys was their ability to influence the behavior of higher status members through responses directed to a 3rd party and other elaborate social strategies, many of which depended on responding to status relations between 2nd and 3rd parties. The fact that such strategies were only observed in the experienced group is a clear indication that the development of higher orders of social cognition is dependent on early social experience.

Animals↗
PubMed2005

Mitochondrial aldehyde dehydrogenase polymorphism is not associated with incidence of Alzheimer's disease.

BACKGROUND: The association between the mutant allele of mitochondrial aldehyde dehydrogenase (ALDH2*2) and Alzheimer's disease (AD) has been controversial and only so far investigated in cross-sectional studies. This study aimed to investigate the longitudinal association between ALDH2*2 and incidence of AD. METHODS: Of 592 participants aged 65 or over without dementia at baseline, 510 (86%) were re-evaluated after 2.4 years and comprised the study sample. Baseline measures included: demographic characteristics, drinking behavior, cognitive function (MMSE), clinical diagnoses of dementia and AD, and genotype (ALDH2 and apolipoprotein E). At the follow up examination, alcohol related characteristics, MMSE and clinical diagnoses of dementia and AD were reassessed. RESULTS: There were no significant associations between the ALDH2*2 and any cognitive outcomes (incidence of dementia or AD, or cognitive decline). These findings were not changed after adjustment for alcohol consumption. No interaction was found between ALDH2 and apolipoprotein E. CONCLUSIONS: ALDH2*2 does not seem to be important in the etiology of dementia.

Aged↗
PubMed2005

Scanning of genetic effects of alcohol metabolism gene (ADH1B and ADH1C) polymorphisms on the risk of alcoholism.

Alcoholism is a multifactorial and polygenic disorder involving complex gene-to-gene and gene-to-environment interactions. Alcohol metabolism is one of the biological determinants that could significantly be influenced by genetic polymorphisms in alcohol-metabolism genes. These genetic polymorphisms are believed to influence drinking behavior and development of alcoholism. Direct DNA sequencing of whole ADH1B and ADH1C genes revealed 36 sequence variants, including six nonsynonymous and 14 novel polymorphisms. Seventeen polymorphisms among them were selected for genotyping in a larger study (n = 352) based on linkage disequilibria (LDs) among SNPs, locations, and frequencies. Hardy-Weinberg equilibrium (HWE) analyses of polymorphisms revealed severe deviations only in alcoholics, which strongly suggest that a selection bias (or pressure) may be involved. The analyses of genotype distribution in alcoholics (n = 106) and normal controls (n = 246) showed dramatic associations with the risk of alcoholism. Fourteen polymorphisms in ADH1C and ADH1B showed a series of different strengths of association and magnitudes of risk. Based on referent and subgroup analysis, it was strongly suggested that the genetic effects come from the ADH1B*47Arg/*47Arg genotype, and that the positive signals from other sites are just tracking the genetic effect of ADH1B His47Arg. In this article we present summaries of previous studies and of the present study, to give an overview of the worldwide effects of ADH1B His47Arg on the risk of alcoholism. The information derived from this study could be valuable for understanding the genetic factors involved in the risk of alcoholism and facilitate further investigation in other ethnic groups.

Adult↗
PubMed2003

Bladder filling by autologous urine production during cystometry: a urodynamic pitfall!

AIMS: The rate of autologous urine production should not have a major disturbing influence on cystometric urodynamic parameters such as first filling sensation, normal desire to void, strong desire to void, and cystometric bladder capacity. Instructions to patients and drinking behavior can have considerable impact, especially if filling cystometry is preceded by free uroflowmetry. We studied the influence of autologous urine production during filling cystometry on total bladder volume. METHODS: Urodynamic investigations performed between September of 2000 and February of 2001 were analyzed. Only those urodynamic investigations for which total bladder capacity could be calculated were taken into account (i.e., catheterization before and after cystometry and no urine loss during the investigations). RESULTS: After screening, 186 investigations were used for further analysis. Mean filled volume (external infusion plus autologous urine production) was 346 +/- 152 mL, but mean real bladder capacity (i.e., voided volume + residual urine) was 391 +/- 170 mL. In all patients, 14% extra urine was produced due to autologous urine production (mean filling rate, 6.1 mL/min). In 42% of the investigations, the real bladder capacity was more than 110% of the infused volume. In 18% of the patients, the contribution of natural bladder filling was more than 25% of the infused volume. CONCLUSIONS: Natural bladder filling plays a substantial role during filling cystometry and has a disturbing influence on calculated urodynamic parameters. Attention should be paid to patient instructions before the urodynamic investigation. The combination of free uroflowmetry followed by filling cystometry should be avoided. This avoidance is especially important if interventional studies are performed. Careful interpretation of studies depending on bladder capacity parameters is mandatory, and such parameters should be corrected for autologous bladder filling.

Algorithms↗
PubMed2002

Noncholinergic actions of atropine on GABAergic synaptic transmission in the subfornical organ of rat slice preparations.

Actions of atropine on GABAergic inhibitory postsynaptic currents to neurons in the subfornical organ, which is a circumventricular organ, were studied by using rat slice preparations with whole-cell clamp recordings. Atropine at 0.01-1 microM antagonized the decreased frequency of Inhibitory postsynaptic currents by carbachol (Xu et al., Am. J. Physiol. Integr. Comp. Physiol. 280, R1657-R1664, 2001). It acted as a muscarinic antagonist at relatively low concentrations. Although the low concentrations of atropine did not change frequency and amplitude of the inhibitory postsynaptic currents, atropine at 10 microM to 1 mM did decrease them in a dose-dependent manner. Glutamatergic excitatory postsynaptic currents were not influenced by atropine at 100 microM. Atropine at 100 microM suppressed GABA- and muscimol-induced outward currents, but not kainic acid-induced inward currents. In addition, decrease of membrane conductance and induction of inward currents by 100 microM of atropine at a holding membrane potential, -51 mV, were found in subfornical organ neurons. From voltage-current curves, a mean reversal potential was estimated to be -65.9 +/- 3.7 mV, near to an equilibrium potential of chloride channels. These imply that atropine at 100 microM suppresses openings of chloride channels. Taken together, it is suggested that, while atropine at low concentrations has an antagonistic action on muscarinic responses, atropine at high concentrations suppresses GABAergic synaptic transmission in subfornical organ neurons. These findings may be of considerable value in understanding the central mechanisms of extraordinary drinking behavior in atropine intoxication.

Animals↗
PubMed1979

Immunocytochemical identification of vasopressinergic and oxytocinergic neurons in the hypothalamus of the cat.

Our immunocytochemical investigation of the magnocellular neuroendocrine cells in the cat hypothalamus reveals a mixture of vasopressin (VP)- and oxytocin (OT)-containing neurons in the supraoptic (NSO), the paraventricular (NPV) and in five accessory nuclei (NAC). We describe the lateral hypothalamic nucleus (NLH), a new accessory nucleus, lying at the junction of the internal capsule and pallidum, and possibly involved in drinking behavior. Previously characterized incompletely in mammals, the four other accessory nuclei consist of the circularis (NC), anterior fornical (NAF), posterior fornical (NPF) and retrochiasmatic (NRC). The two peptidergic cell types, VP and OT, are equally mixed in the NPV and the NAC, but in the NSO VP neurons predominate. The perikarya of these VP and OT neurons do not show distinct morphological differences at the level of light microscopy. The organization of magnocellular neuroscretory neurons in the cat hypothalamus closely resembles that described in other mammals with the exception of the unique presence of the lateral hypothalamic accessory nucleus.

Animals↗
PubMed1979

The effect of housing and gender on preference for morphine-sucrose solutions in rats.

To determine whether opiate consumption is affected by laboratory housing, individually caged and colony rats were given a choice between water and progressively more palatable morphine-sucrose solutions. The isolated rats drank significantly more of the opiate solution, and females drank significantly more than males. In the experimental phase during which morphine-sucrose solution consumption was greatest, the isolated females drank five times as much, and the isolated males sixteen times as much morphine (mg/kg) as the colony females and males respectively.

Animals↗