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H Kalant

Publications and source records attributed to H Kalant.

At least 109 records · Page 6Linked to original sources
PubMed1984

Temporal correlation of changes in rat brain sialic acid and in inhibition of Na+-K+ ATPase with ethanol tolerance.

Administration of ethanol to rats by gavage, in daily doses increasing gradually from 3 to 6 g/kg, led to progressive development of tolerance to the hypothermic effect of test doses of ethanol (3 g/kg, i.p.), between days 4 and 21 of treatment. Tolerance was decreased by day 3 of withdrawal, and had disappeared by day 7. Basal levels of brain microsomal Na+-K+ ATPase activity increased progressively during tolerance development, and returned to normal by 4 days after ethanol withdrawal. Conversely, inhibition of the ATPase by ethanol alone (0.22-0.66 M), or by 1 microM norepinephrine (NE) combined with much lower concentrations of ethanol (0.0125-0.1 M), decreased progressively during tolerance development, and returned to normal after withdrawal. The best temporal correlation with the degree of tolerance was shown by the magnitude of NE sensitization of the enzyme to ethanol inhibition. The chronic sucrose control treatment resulted in an unexplained increase in the NE sensitization. Since synaptosomal membrane concentration of sialic acid showed a similar time course during ethanol treatment, it is possible that changes in membrane sialic acid contribute to the alteration in NE sensitization by altering NE receptor properties.

Animals↗
PubMed1984

Effect of ethanol tolerance on norepinephrine-ethanol inhibition of (Na+ + K+)-adenosine triphosphatase in various regions of rat brain.

Brain (Na+ + K+)-adenosine triphosphatase activity from untreated rats was inhibited by a combination of 1 microM norepinephrine + 50 mM ethanol (NE + EtOH), in preparations from cerebral cortex (CX), cerebellum (CB), hippocampus (HC), hypothalamus (HT), thalamus-midbrain and pons-medulla, but not from striatum. The rank order of inhibition in these regions was more similar to that of alpha-1 receptor density than of regional NE content. EtOH administration for 3 weeks produced tolerance to the hypothermic effect of EtOH; increased basal adenosine triphosphatase activity in CX, CB and HC, as measured 24 hr after withdrawal; and decreased the inhibitory effect of NE + EtOH in CX, HT, HC and CB preparations. Tolerance to the inhibitory effects of high concentrations (0.22 or 0.44 M) of EtOH alone was found only in CX, HT and HC preparations. Tolerance to NE + EtOH or to EtOH alone was greatest in HC and CX, intermediate in HT and CB and least or absent in other regions. Temperature-dependence of (Na+ + K+)-adenosine triphosphatase activity was studied in preparations from CX (high initial sensitivity to NE + EtOH, high tolerance development), CB (intermediate initial sensitivity, intermediate tolerance) and striatum (no initial sensitivity, no tolerance). Arrhenius plots showed differences between these regions, with respect to changes in transition temperature and activation energy after chronic EtOH treatment in vivo. These changes did not explain the regional differences in tolerance development. Therefore it seems unlikely that a single mechanism, such as "stiffening" of the cell membrane, can explain the varied pattern of tolerance development in different brain regions.

Animals↗
PubMed1983

Behavioral effects of prolonged administration of delta 9-tetrahydrocannabinol in the rat.

Rats treated chronically with delta 9-tetrahydrocannabinol (THC, daily oral dose 20 mg/kg) were examined for residual effects on a variety of behaviors following a 1-4-month drug-free period. Learning a 12-arm radial maze and a differential reinforcement of low-rate responding (DRL-20) task was significantly retarded in THC-treated animals, although performance reached control levels by the end of testing. Learning two-way shuttle box avoidance was slightly facilitated in the drug-treated subjects. In open field tests THC-treated rats displayed an initial hypoactivity, followed by hyperactivity, but these changes were not significant. Most of the effects of THC resemble, but are weaker than those of chronic treatment with cannabis extract in a dose containing the same amount of THC. The findings are discussed in terms of the role of other constituents of cannabis that may add to, or potentiate the effects of THC itself.

Animals↗
PubMed1983

Differential pharmacological responses to ethanol, pentobarbital and morphine in rats selectively bred for ethanol sensitivity.

The hypothermic and analgesic effects of ethanol, pentobarbital and morphine were examined in two lines of rats that had been selectively bred for their differential sensitivity to ethanol. Males and females of the least-affected (LA) line were observed to be less sensitive than their most-affected (MA) counterparts to hypothermia and analgesia induced by ethanol and morphine. By contrast, no differences were observed with respect to pentobarbital-induced hypothermia. At the dose used, pentobarbital had no significant analgesic effect in either animal line.

Analgesics↗
PubMed1983

Motivational properties of ethanol in naive rats as studied by place conditioning.

The reinforcing properties of ethanol were examined in naive adult male rats by means of a place conditioning paradigm that has previously demonstrated the positive reinforcing properties of food, water and some drugs, and the aversive properties of punishers such as electric shock and lithium chloride. Only doses of 0.8-1.0 g/kg and higher produced clear place conditioning, and this was only conditioned place aversion; rats spent significantly more time on the side of the place conditioning box in which they received the vehicle than on the side in which they received ethanol. Doses between 0.1 g/kg and 0.8 g/kg produced increases in general activity, but did not produce any place conditioning. Control experiments indicated that the pattern of effects was not specific to the route of ethanol administration (intravenous or intragastric), rate of infusion, concentration, or vehicle. It was concluded that ethanol, in the doses used here, has only punishing or neutral motivational effects in naive rats and does not serve as a primary positive reinforcer in this model. The conclusions are discussed in relation to the relative difficulty encountered in attempts to produce ethanol self-administration, and the findings are viewed as consistent with a proposal that prolonged training and experience with ethanol are important for ethanol self-administration by the rat.

Alcoholism↗
PubMed1983

Brain synaptosomal (Na+ and K+)ATPase activity as an index of tolerance to ethanol.

Variations of brain synaptosomal (Na+ and K+)ATPase activity and development of functional tolerance to ethanol were followed simultaneously throughout a chronic ethanol treatment. Inhibition of the enzyme activity by ethanol added in vitro in the presence of noradrenaline was also assayed. Adult male rats were rendered tolerant to ethanol by daily intragastric administration of doses of 3-6 g of ethanol/kg body wt. As assessed by the hypothermic effect and impairment of motor performance on a tilting plane after injection of a challenge dose of ethanol (3 g/kg body wt. IP), functional tolerance developed slowly, was demonstrable after 2 weeks of treatment and increased for up to 4 weeks. The two tolerance tests gave parallel and positively correlated results. Concurrently with the development of tolerance, the basal activity of brain synaptosomal (Na+ and K+)ATPase increased (7% to 18%) in preparations from ethanol treated animals when compared to those from starch-fed caloric controls, and there was less inhibition of the enzyme by ethanol added in vitro in the presence of noradrenaline. The time course of the appearance of these changes in enzyme activity were positively correlated with that of behavioral tolerance, strengthening a relationship between the phenomena events. The intensity of the noradrenaline-ethanol interaction with the membrane-bound (Na+ and K+)ATPase activity could be an index of the degree of tolerance to ethanol.

Alcoholism↗
PubMed1983

Effects of ethanol on thermoregulation.

Clinical reports of accidental hypothermia in alcohol intoxicated individuals exposed to low ambient temperature ( Paton , 1983) have generally been borne out by experimental studies in healthy volunteers. Small doses of ethanol, given to human subjects at normal ambient temperature (Ta), have very little effect on body temperature but a combination of large dose, low Ta and vasodilatation provoked by strenuous exercise, causes a sharp fall in rectal temperature. In experimental animals, the use of relatively larger doses of alcohol and more extreme temperatures, both above and below the thermoneutral zone, has shown that the effect of ethanol is essentially poikilothermic, i.e. an impairment of adaptation to both heat and cold. This effect has been studied in greater detail, in relation to each of the basic thermoregulatory processes. Though small doses of alcohol may increase the metabolic rate under some circumstances, the most common effect at low Ta is inhibition of shivering and therefore reduction of thermogenesis. At the same time it tends to cause increased heat loss by cutaneous vasodilatation. This makes for a greater feeling of comfort in the cold exposed subjects but increases in rate of fall of core temperature. The combination of decreased thermogenesis and increased heat loss, despite falling body temperature, is suggestive of a lowering of the set-point of the thermoregulatory control mechanisms. Consistent with this is a slight increase in ventilatory heat loss after low doses of ethanol but larger doses cause respiratory depression, so that heat loss through the lungs is minor. However, at high Ta ethanol caused hyperthermia in experimental animals and shows enhanced lethality, so that impairment of thermoregulatory effector mechanisms seems to be at least as important as change in set-point. Studies of the effects of ethanol on electrophysiological activity of single neurons in the pre-optic area and anterior hypothalamus (POAH), biochemical activities of neuronal membranes, hypothalamic blood flow, conventional neurotransmitters, amino acid putative neurotransmitters, neuropeptides, prostaglandins and inorganic ions have all failed so far to yield a clear comprehensive picture of the mechanisms by which ethanol affects thermoregulation. In each case, contradictory evidence has been obtained concerning the consequences of ethanol administration, whether by oral, intraperitoneal, intravenous, intracerebroventricular, or direct local (POAH) route.(ABSTRACT TRUNCATED AT 400 WORDS)

Alcoholism↗
PubMed1983

Chronic ethanol treatment alters the biosynthesis of beta-endorphin by the rat neurointermediate lobe.

Tolerance to ethanol was induced in male Sprague-Dawley rats (225-250 g) by chronic feeding with a liquid diet containing 6.5% ethanol (v/v). Control rats were pair-fed with a liquid diet in which the ethanol was replaced by an equicaloric concentration of sucrose. Immediately following sacrifice of the animals the neurointermediate lobes (NIL) were removed and incubated with [3H]phenylalanine. The biosynthesized proopiomelanocortin (POMC), beta-lipotropin (beta-LPH), and beta-endorphin (beta-EP) were purified by immunoprecipitation with an antiserum to beta-EP and analyzed by sodium dodecyl sulfate polyacrylamide disc gel electrophoresis. Alcohol treatment for 3 days had no effect on the degree of incorporation of [3H]phenylalanine into POMC, beta-LPH, and beta-EP but treatment for either 15 or 21 days increased the incorporation of [3H]phenylalanine into all three peptides. Ethanol treatment also increased the beta-endorphinlike immunoreactivity (beta-EPLIR) found in the incubation medium, but no significant change was observed in the beta-EPLIR extracted from the NIL either immediately after sacrifice or after 3 h of incubation of the NIL. However, a significant decrease of beta-EPLIR was found in the anterior lobes of rats treated with ethanol for 21 days. Furthermore, the beta-EPLIR in the serum of alcohol-treated rats was significantly higher than in the serum of their corresponding controls. These results indicate an effect of ethanol on the endorphin system and are consistent with the suggestion that endorphins may be mediators of some of the ethanol effects.

Animals↗
PubMed1982

Interaction between des-glycinamide9-[Arg8]vasopressin and serotonin on ethanol tolerance.

Sham and electrolytic lesions of the dorsal, median, and dorsal + median raphe nuclei were made in different groups of rats. One week later, daily oral treatment with ethanol (5 g/kg p.o. for 25 days) was started. This treatment produced tolerance to the hypothermic and motor impairing (moving belt test) effects of ethanol. On day 26, ethanol was stopped and subcutaneous injection of either 10 micrograms of des-Gly9-[Arg8]vasopressin (DGAVP) in saline or saline alone was started. The retention of tolerance to ethanol was measured at 3-day intervals for both hypothermia and motor-impairment. In sham-saline groups, disappearance of tolerance took 3 days for the hypothermic effect, and 9 days for the motor-impairment effect. Tolerance to both effects, however, was still observed after 9 days in DGAVP-treated rats with either sham or dorsal raphe lesions. Peptide treatment, on the other hand, failed to maintain tolerance in rats with median or median + dorsal raphe lesions. These results suggest that an intact mesolimbic serotonin pathway is necessary for the action of DGAVP on the retention of ethanol tolerance.

Animals↗
PubMed1982

Learning impairment in the radial-arm maze following prolonged cannabis treatment in rats.

Chronic oral administration of cannabis extract to rats (daily delta 9-tetrahydrocannabinol dose 20 mg/kg) was examined in three experiments for its residual effect on radial-arm maze learning following a 1-month drug-free period. Learning a simple eight-arm maze was significantly impaired in rats treated for either 6 months (Experiment I) or 3 months (Experiment II) with the drug. In Experiment III, animals that received the extract for 3 months exhibited significant learning deficits on a much more difficult 12-arm radial maze. The results demonstrate that the deleterious effects of cannabis on radial-arm maze learning are probably due to a tendency toward increased vigilance and perseveration, possibly combined with an impaired utilization of spatial cues.

Animals↗
PubMed1982

Residual effects of prolonged cannabis administration on exploration and DRL performance in rats.

Chronic oral administration of cannabis extract to rats (daily delta 9-tetrahydrocannabinol dose 20 mg/kg) was examined for its residual effect on open field activity and DRL (differential reinforcement of low-rat responding) performance, following a 2-3 month drug-free period. Locomotor activity during the latter part of an open field test was markedly increased in rats previously treated for either 6 months or 3 months with the drug. The same treatments also produced a significant impairment on a DRL-20 task relative to control subjects' performance. These and other findings (impaired maze learning and facilitated two-way shuttle box avoidance) might mean that cannabis produces long-lasting hippocampal dysfunction in rats.

Animals↗
PubMed1982

Factors involved in the differential response to ethanol, barbital and pentobarbital in rats selectively bred for ethanol sensitivity.

Two lines of rats, 'least affected' (LA) and 'most affected' (MA), had been selectively bred for their differential sensitivity to ethanol. Both males and females of the LA strain were observed to be less sensitive than their MA counterparts to the acute hypnotic and motor-impairing effects of ethanol. However, a lower ethanol metabolic rate of the MA males suggests that both CNS and metabolic factors contribute to their enhanced sensitivity to ethanol. By contrast, no differences were observed between the LA and MA males with respect to the hypnotic and subhypnotic effects of pentobarbital or to the clearance of this drug. MA females were more sensitive only to the hypnotic effects of pentobarbital, probably because of a smaller apparent volume of distribution. No strain difference was observed in the hypnotic effect or clearance of barbital. These observations suggest that, in spite of a differential sensitivity to ethanol, the LA and MA lines do not differ in their response to the barbiturates tested.

Animals↗
PubMed1982

Effect of naloxone on ethanol- and pentobarbital-induced narcosis.

Single or repeated subcutaneous administrations of naloxone in doses of up to 4 mg X kg-1 did not alter the time for onset or the duration of ethanol- or pentobarbital-induced narcosis in rats. An increase in the naloxone dosage to 50 mg X kg-1 s.c. resulted in a small reduction of ethanol-induced sleep duration. Repeated i.p. or i.v. administrations of much higher doses of naloxone (300-400 mg X kg-1 and 120-180 mg X kg-1, respectively) did produce significant reductions in ethanol-induced narcosis. However, similar naloxone doses, when administered alone, i.v., had marked convulsant effect. It appears that naloxone, in low doses, is not an effective antidote for narcosis caused by ethanol or pentobarbital at the ethanol and pentobarbital doses tested, whereas the antagonism of ethanol-induced sleep by high doses of naloxone may be due to the analeptic action of this drug.

Animals↗
PubMed1982

Effect of chronic ethanol treatment on temperature dependence and on norepinephrine sensitization of rat brain (Na+ + K+)-adenosine triphosphatase.

Rat brain (Na+ + K+)-adenosine triphosphatase is inhibited by ethanol (EtOH) in vitro, the inhibition being greater in the presence of norepinephrine (NE). Enzyme preparations from EtOH-tolerant rats show less inhibition by EtOH in vitro and less sensitization by NE. To investigate the mechanism of these changes, the enzyme activity of brain microsomes from tolerant and sucrose-control rats was measured at temperatures from 10-40 degrees C. Preparations from nonwithdrawn and 24-hr withdrawn rats were studied in the absence of in vitro additions, and in the presence of 1 microM NE, 50 mM EtOH or 440 mM EtOH separately, and of 1 microM NE + 50 mM EtOH. From Arrhenius plots of the results, the transition temperature (Td) was calculated by a method of successive approximations, and the activation energies were calculated from the segments above and below Td. Chronic EtOH treatment significantly decreased Td, but increased activation energies below Td. These findings suggest different effects on membrane matrix lipids than on boundary lipids adjacent to the enzyme. However, EtOH-tolerant preparations showed less effect of EtOH in vitro than did control preparations, on both Td and activation energies. Preparations from EtOH-tolerant and withdrawn rats behaved almost identically, indicating that the changes accompany tolerance and are not withdrawal effects. NE + 50 mM EtOH produced the same effects as 440 mM EtOH alone, in all preparations. EtOH tolerance reduced the sensitizing effect of NE. EtOH is interpreted as affecting both the boundary lipids and the apoenzyme itself.

Animals↗