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L A Pohorecky

Publications and source records attributed to L A Pohorecky.

At least 19 recordsLinked to original sources
PubMed1992

Daily dose of ethanol and the development and decay of acute and chronic tolerance and physical dependence in rats.

Using behavioral and physiological measures, we compared the rates of development and decay of acute and chronic tolerance to ethanol (ET) and the severity of the withdrawal syndrome. Male rats were treated with 6, 9, or 12 g/kg/day ET or equicaloric dextrin maltose, delivered intragastrically. Although treatment duration varied, the total dose of ET was kept constant at 162 g/kg/rat for the three groups. The effects of a cumulative test dose of ET or equicaloric dextrin maltose, after exposure to a total of 0, 42, 83, 126, and 162 g/kg ET, and at 3, 5, and 7 days after termination of the chronic treatments, were evaluated on rectal temperature, dowel performance, and tail-flick and startle responses. After the initial five tolerance tests, chronic treatments were discontinued and rats were tested in a modified open-field apparatus and for their startle response to an auditory stimulus at 8, 12, 16, 20, 32, and 40 h later. With all measures, little tolerance developed in the 6-g/kg/day group. On the other hand, development of chronic tolerance was fastest in rats treated with the 12-g/kg/dose of ET. Chronic tolerance did not develop to ET's depressant effect on the startle response. Acute tolerance declined with chronicity of treatment in animals given the largest daily dose of ET. During withdrawal, and in contrast to the dextrin maltose-treated animals, there was impairment in all measures taken during the modified open-field test and hypersensitivity of the startle response for all three chronic ET-treated animals. Greatest behavioral impairment occurred in animals treated with 12 g/kg/day, and some impairment was still evident 40 h after the last dose of ET. Thus, the severity of the withdrawal syndrome was greatest in the group displaying the most acute and chronic tolerance.

Alcoholic Intoxication↗
PubMed1992

Zacopride, a 5-HT3 receptor antagonist, reduces voluntary ethanol consumption in rats.

The effect of the selective 5-HT3 receptor antagonist, zacopride, was assessed in male Sprague-Dawley rats in free choice (6% ethanol and water) experiments. In Experiment 1, single zacopride (0.01-10 mg/kg, IP) injections failed to alter ethanol (ET) consumption during 1-h restricted ET access. In Experiment 2, zacopride (5.0 and 10 mg/kg, IP) injected twice daily for 5 days significantly reduced ET intake and ET preference during 24-h free access to 6% ET and water without altering the total volume of fluid consumed. Thus, the schedule of ET access (i.e., free vs. restricted) and/or the duration of drug treatment may determine the efficacy of pharmacological agents in altering ET preference. 5-HT3 receptor blockade may reduce serotonin/dopamine-mediated maintenance of ET preference; a process that may proceed via extinction mechanisms.

Animals↗
PubMed1991

Stress and alcohol interaction: an update of human research.

The literature on alcohol and stress in human subjects carried out since 1981 is reviewed. The review covers selected aspects of the interaction of alcohol and stress. (1) Most of the review focuses on the role of stress on alcohol ingestion. Retrospective research based on data from the Health and Nutrition Examination Survey indicated an increase in alcohol consumption with anxiety in certain groups of, as yet not well characterized, individuals. For example, although still insufficiently documented, stress does not appear to play a significant role in alcohol ingestion by women and the elderly. By contrast, stress does appear to play a role in the control of alcohol ingestion by adolescents. Prospective studies employing questionnaire-interview formats generally support an effect of stress on alcohol ingestion. However, studies employing male college aged social drinkers did not find a correlation between levels of stress and ingestion of alcohol. Alcoholics also differ in the reasons for drinking alcohol, but generally ingest alcohol to lessen anxiety/stress. It is clear that the Tension Reduction Hypothesis as originally postulated is no longer adequate. Many new models based on an interaction of alcohol and stress have been proposed to explain the control of alcohol consumption. Considering the multidimensionality of factors that appear to contribute to the control of alcohol ingestion, it is unlikely that a single model could possibly be relevant to alcohol ingestion under all conditions. More likely different models may be relevant to alcohol consumption under specific conditions, or for specific populations. (2) Alcohol has been reported to decrease anxiety in agoraphobics. The self-medication by agoraphobics may contribute significantly to their alcohol abuse. (3) Alcohol has also been reported to decrease tremor of the hands in stressed subjects as well as in patients with essential tremor. (4) Although a number of studies have employed electrodermal activity in studies aimed at the interaction of alcohol and stress, the results have been rather inconsistent. (5) The controversy on the purported beneficial effect of alcohol on the cardiovascular system persists. A number of studies have shown a J- or U-shaped relationship between alcohol ingestion and incidence of coronary heart disease. Alcohol may also influence stress-induced changes in blood pressure. Although a number of studies have demonstrated lower blood pressure in individuals ingesting less than two drinks per day compared with abstainers or heavy alcohol imbibers, the evidence is not conclusive. (6) It is not clear whether the interaction of alcohol and stress involves alterations in plasma catecholamines.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1991

Development of tolerance to and physical dependence on ethanol: daily versus repeated cycles treatment with ethanol.

We examined the effect of various treatment schedules with ethanol on the development of tolerance and the severity of withdrawal in rats. Tolerance to ethanol was examined after a challenge dose of ethanol using rectal temperature, dowel performance, and tail flick response; open field activity and the startle response were determined during withdrawal. Animals treated daily with ethanol developed greater tolerance, and also lost it faster, compared with animals subjected to repeated cycles of 3 days of ethanol treatment followed by 3 drug-free days. Also, the severity of withdrawal was greater in animals treated daily with ethanol. In the second study, we examined the development of tolerance and withdrawal severity of animals subjected to three different schedules of daily ethanol administration. Overall, the animals receiving continuous infusion of ethanol showed the most severe withdrawal and had, except for dowel performance, the fastest loss of tolerance to ethanol.

Alcohol Drinking↗
PubMed1990

Interaction of ethanol and stress: research with experimental animals--an update.

Research on the interaction of ethanol (ET) and stress published since 1981 is reviewed. Chronic physical stressors were found to increase the ingestion of ET compared to nonstressed animals. With foodshock, ingestion of ET decreased during the stress session but rose afterwards. The elevation of ET ingestion produced by daily immobilization was long-lasting and was related to individual initial preference for ET. Psychological stressors also increased ingestion of ET. In rat colonies, dominant rats ingested less ET, whereas submissive rats had the highest intake. Factors that modify the ingestion of ET include neonatal experience and REM sleep deprivation. Early weaning increased, while postnatal handling decreased preference for ET. The effect of postnatal handling may be influenced by genetics. Stress, applied during adult life or prenatally, modifies some, but not all, the acute effects of ET. There were marked individual differences in the interaction of ET and stress with respect to ingestion of ET. Conversely, ET may modify stress-induced behavioural and neurochemical changes. This interaction may be stressor specific. Some stressors increase the ET's effects, whereas others may decrease or not affect them. In brain, ET has been shown to lessen the stress-induced decrease in noradrenaline and 5-hydroxytryptamine (serotonin) levels and those in noradrenaline turnover and alpha 1-receptor binding. Stress-induced changes in plasma catecholamines, corticosterone, non-esterified fatty acids and amino acids, and in the decline in adrenal catecholamines are also lessened by pretreatment with ET. Possible mechanisms for the ET-stress interaction are discussed. These include mediation via the GABA-benzodiazepine-ionophore complex, endogenous opioids, the hypothalamo-pituitary-adrenocortical axis and the noradrenergic system.

Alcohol Drinking↗
PubMed1989

Norepinephrine-induced diuresis in chronically ethanol-treated rats.

Previous research from this laboratory indicated that noradrenergic mechanisms might mediate ethanol diuresis. Experiments described here examined changes in sensitivity of noradrenergic mechanisms in animals chronically treated with ethanol. Norepinephrine hydrochloride (0-12 micrograms intracerebroventricularly) produced dose-dependent diuresis in control (dextrin maltose) and ethanol (8-11 g/kg/day) treated rats on the first day of treatment. Tolerance to ethanol diuresis was present after 10 days of ethanol treatment. Lack of responsiveness to norepinephrine-induced diuresis was evident only on the 20th day of treatment in both the ethanol and dextrin-maltose groups of rats. These results indicate a temporal dissociation between the tolerance to ethanol-induced and norepinephrine-induced diuresis and suggest that norepinephrine may not play a primary role in the development of tolerance to the diuretic action of ethanol.

Animals↗
PubMed1989

Effects of ethanol on plasma corticosterone and rectal temperature modification by U50488H and WIN 44441-3.

Endogenous opiates are believed to subserve various behaviors and physiological functions. We have examined the effect of U50488H (0-12 mg/kg), a kappa agonist, and WIN 44441-3 (0-4.0 mg/kg), a kappa antagonist, on ethanol (ET)-induced changes in rectal temperature and in plasma corticosterone (CS) levels in rats. The 12 mg/kg dose of U50488H produced marked hypothermia, the other doses either produced hyperthermia comparable to that seen in control animals, or had no effect. The 0.5 mg/kg of WIN44441-3 had a small hypothermic effect while the 4.0 mg/kg produced hyperthermia. U50488H potentiated and the low dose of WIN 44441-3 reversed the hypothermic effect of ethanol. By contrast, neither WIN 44441-3 nor U50488H pretreatments affected the ethanol-induced elevation in plasma CS. These results indicate that kappa agonists increase plasma CS concentration and affect thermoregulatory mechanisms. Furthermore, our data indicate a possible role of endogenous kappa opioids in the hypothermic effect of ethanol, but not in the elevation of plasma CS.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1989

Effects of ethanol in an open field apparatus: modification by U50488H and WIN 44441-3.

The effects of U50488H, a kappa agonist, and WIN 44441-3, a kappa antagonist, and their modification of the effects of ethanol, on the behavior of rats in a modified open field apparatus, was examined. Crossover activity was increased by U50488H. Headpoke activity was decreased by WIN 44441-3 and increased by U50488H. Rearing activity was increased by WIN 44441-3 but was not affected by U50488H. The effect of both drugs was dose related, with the largest doses having no effect. Ethanol (0.5 g/kg) stimulated crossover activity while it depressed rearing, headpoke and corner activities; except for crossover activity the 2.0 g/kg dose of ethanol depressed these activities. Pretreatment with WIN 44441-3 (0.5 mg/kg) potentiated the stimulant effect of ethanol on crossover activity and partially reversed the depressant effect of ethanol on rearing and headpoke activities. U50488H potentiated the ethanol-induced depression of headpoke and reversed the depression of corner activity. Pretreatment with U50488H had no effect on ethanol's action on crossover and rearing behaviors. Our results indicate that kappa opiate receptors may mediate some behaviors exhibited by rats in a modified open field apparatus. Activation of these receptors increases locomotor and headpoke activity but had no effect on rearing activity. Furthermore, the 0.5 g/kg dose of ethanol has differential effects on different measures of open field behavior, while the 2.0 g/kg dose was largely depressant. Our data suggest that some of these effects of ethanol may be mediated via kappa opioid receptors.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1989

Neuroendocrine and beta-adrenoceptor response to chronic ethanol and aggression in rats.

Male rats were administered either ethanol (6-8 g/kg/day) or dextrin-maltose, an isocaloric equivalent, for two weeks prior to a 24-hour resident-intruder test. After the first 20 minutes of the aggression test residents showed a greater increase in norepinephrine than intruders (216% vs. 97%), while intruders showed a greater increase in epinephrine (394% vs. 51%) and corticosterone (338% vs. 129%) than residents. Ethanol administration increased the initial epinephrine response of intruders almost two-fold compared to dextrin-maltose intruders. After 24 hours of aggression testing plasma norepinephrine was still elevated in residents (92%) and intruders (71%), however, only intruders continued to show an elevation in plasma corticosterone (98%) and epinephrine (107%). Using a cumulative dose-response technique, the dose of isoproterenol required to produce 50% of the maximal heart rate response (ED50) increased in intruders by 108% following aggression testing with ethanol intruders showing significantly smaller mean change. The increase in ED50 was related to drug type, behavior, and plasma corticosterone and epinephrine levels. Rats treated with ethanol had a greater beta-adrenoceptor density than control rats. However, no relationship was found between receptor density and the other measures in this study.

Aggression↗
PubMed1989

Alteration of the effects of caffeine by prenatal stress.

We examined the effect of prenatal stress exposure on sensitivity to caffeine using behavioral and physiological measures. Pregnant rats were handled 5 minutes daily from the 14th to 21st day of gestation. Male offspring were tested when 60 days of age in a modified open field apparatus 30 and 90 minutes after injection with caffeine (0, 10, 30 mg/kg). Caffeine increased crossover frequency and duration at the 10 mg/kg dose. Rearing frequency and duration were increased by the 10 mg/kg dose while the 30 mg/kg dose was ineffective. Gnawing was increased by caffeine, especially 90 minutes postinjection. Headpoke activity was decreased by caffeine treatment. Caffeine had no effect on defecation and urination. Gnawing activity was increased by caffeine in prenatally nonstressed animals, but was depressed in prenatally stressed animals. Prenatal stress increased sensitivity to caffeine on corner activity and rearing. The other measures were not affected differentially by prenatal stress exposure. Rectal temperature was depressed 0.75 degrees C in both prenatally stressed and nonstressed animals, by the 30 mg/kg dose of caffeine. Thus, our results indicate that prenatal stress affects sensitivity to caffeine in the adult offspring. However, the long-term effects of prenatal stress exposure are dependent on the measures employed.

Animals↗
PubMed1989

The effect of repeated withdrawal episodes on subsequent withdrawal severity in ethanol-treated rats.

Male rats were given ethanol via an intragastric catheter (8.0-11.0 g/kg per day) for either 8 weeks daily or for four 2-week periods with a 2-week period of no drug treatment intervening between each period of ethanol administration (binge). Older rats were administered ethanol for 2 weeks, to assess the effects of age on ethanol withdrawal as age can alter an animal's sensitivity to ethanol. The presence of physical dependence during withdrawal was assessed on an open field test. Rats that experienced repeated episodes of withdrawal (binge) showed more severe withdrawal signs in successive withdrawal episodes. Older animals showed more severe signs of withdrawal than younger animals after 2 weeks of ethanol treatment. The results of this study lend support to the hypothesis that the experience of withdrawal from ethanol can alter an animal's subsequent response to the drug. Aging appeared to contribute to this effect, but further work is needed to delineate its role.

Aging↗
PubMed1988

Factors modifying the effect of diazepam on plasma corticosterone levels in rats.

We have examined factors that alter the effect of diazepam (DZ) on plasma corticosterone (CS) in rats. DZ had a biphasic effect on plasma CS levels: CS decreased with doses below 5 mg/kg and increased with higher doses. Peak response occurred 90 minutes post injection in both sexes. Plasma DZ levels were significantly higher in females than in males and peak at 10 and 30 minutes post injection in males and females, respectively. There was also a sex difference in the pattern of DZ metabolites. An acute stressor (30 minutes of immobilization) did not affect plasma CS levels in rats injected with a 5 mg/kg dose of DZ. Prenatally stressed animals did not differ in basal CS levels or in their response to 5 mg/kg of DZ compared to prenatally non-stressed animals. These two groups of animals also did not differ in plasma levels of DZ or of its metabolites. By contrast, the 5 mg/kg dose of DZ had no effect on plasma testosterone levels in control animals, but increased it in prenatally stressed animals. Furthermore, compared to non-stressed controls, prenatally stressed animals had lower baseline plasma testosterone levels. These results indicate that the effect of DZ on plasma CS is influenced by endogenous as well as exogenous factors and that these effects vary with the particular biochemical parameter under examination.

Animals↗
PubMed1988

Interaction of stress and ethanol: effect on beta-endorphin and catecholamines.

To examine the interaction of ethanol (ET) and stress on beta-endorphin and catecholamine (CA) levels, male rats pretreated with ET (3.0 g/kg, i.p.) or saline were immobilized for 30 min and killed 90 min after the initial injection. Stress resulted in (a) an increase in plasma levels of norepinephrine (NE, 243%), epinephrine (E, 175%), beta-endorphin (220%) and corticosterone (CS, 151%) and a decrease in dopamine (DA, 54%); (b) a decrease in hypothalamic NE (15%) and beta-endorphin (33%) levels and an increase E (23%) and DA (58%) levels; (c) a decrease in pituitary beta-endorphin levels in both the neurointermediate (23%) and anterior (131%) lobes. Treatment with ET resulted in: (a) an increase in plasma NE (81%), E (53%), CS (71%), and beta-endorphin (33%) levels and decrease in DA (54%); (b) a decrease in the hypothalamic NE (12%) levels and an increase DA (27%) and beta-endorphin (46%) levels, and (c) a decrease in beta-endorphin (15.5%) in the intermediate lobe of the pituitary. Treatment with ET of stressed animals had only a small effect: (a) in plasma NE, E, CS, and beta-endorphin levels decreased by 30, 31, 14, and 36%, respectively; (b) in the hypothalamus DA levels decreased by 40% and beta-endorphin increased by 71%; (c) in the pituitary beta-endorphin increased in both the intermediate lobe (25%) and anterior (50%) lobes. Thus when the data of the stressed ET-treated group is compared to that of the nonstressed saline injected group, none of the measures differ significantly. These results confirm our earlier work indicating a significant interaction of ET and stress.

Animals↗
PubMed1987

An in vivo cumulative dose-response assay of the myocardial beta-adrenoceptor system.

This paper describes an in vivo computer-based cumulative dose-response assay of the myocardial beta-adrenoceptor system. The technique involves measuring the ability of isoproterenol, a beta-adrenergic agonist, administered through a jugular catheter to increase heart rate in rats. The computer system monitors heart rate, provides real-time graphics of incoming data and a detailed graphic review of responses following testing, coordinates drug injections by the experimenter, performs a nonlinear line analysis to determine the dose required to produce 50% maximal responding (ED50) following the data review, and generates a diskette and printer report at the completion of testing. Data are presented and discussed on how well this system meets the assumptions underlying the cumulative dose-response methodology. The results of a study on the effect of acute footshock on the myocardial beta-adrenoceptor system as measured by this technique is also presented and discussed. This technique permits chronic studies of an important myocardial receptor system and allows receptor changes to be tracked within individual subjects.

Analysis of Variance↗
PubMed1986

The effects of peripherally administered monoaminergic drugs on ethanol diuresis in rats.

The effect of peripherally administered drugs that modify monoaminergic function, on ethanol (2.0 g kg-1, intragastrically)-induced changes in urine output has been examined in rats. The alpha-noradrenoceptor agonist, clonidine (0.05-0.15 mg kg-1) produced marked urine output and potentiated slightly the diuretic effect of ethanol. The alpha-noradrenoceptor antagonist, phentolamine (1-5 mg kg-1) dose-dependently decreased ethanol-induced diuresis. p-Chloroamphetamine (0.8-2.0 mg kg-1) produced significant diuresis and potentiated the diuresis produced by ethanol. Methysergide (1.25, 2.5 mg kg-1), a 5-hydroxytryptamine receptor antagonist, had no effect on urine output while it depressed the ethanol-induced increase in urine output. Apomorphine (0.8, 1.5 mg kg-1), a dopamine receptor agonist, did not modify urine output in either control or ethanol-treated animals, while the dopamine receptor antagonist, pimozide (0.75-3.0 mg kg-1), dose-dependently decreased ethanol-induced diuresis, but had no effect on urine output in control animals. Since our previous research indicates that the intraventricular administration of drugs that alter dopaminergic and 5-HT function does not alter ethanol-induced diuresis, the interaction of these types of agents with ethanol-induced diuresis in the present study suggests that the interaction was mediated peripherally.

Animals↗
PubMed1985

Ethanol diuresis in rats: possible modifying factors.

Ethanol has been shown to produce a biphasic dose-dependent effect on urine output in rats. Experiments were carried out to examine factors which may influence ethanol diuresis. Immobilization stress (30 min) decreased and ethanol (2.5 g kg-1) increased urine output of intragastrically hydrated rats. In stressed rats, ethanol had a more pronounced diuretic effect compared with home cage control rats. This increased sensitivity to ethanol disappeared when rats were immobilized daily for four days, indicating development of tolerance. The diuretic action of ethanol was not influenced by adrenalectomy.

Adrenalectomy↗
PubMed1979

Cholinergic mediation of motor effects of ethanol in rats.

The role of cholinergic neurons in the motor depressant effects of ethanol was examined. Choline chloride pretreatment (30-90 mg/kg i.p.) potentiated the hypomotility produced by 2 g/kg of ethanol. Physostigmine pretreatment (0.2 mg/kg i.p.) also enhanced the motor depression produced by ethanol. Conversely, in animals pretreated with scopolamine (0.25 and 0.5 mg/kg) the depressant effect of ethanol was less. The potentiation produced by choline was not associated with changes in levels of ethanol in blood. It is concluded that cholinergic neurons are involved in the motor activity changes produced by ethanol. Such a mechanism may operate in conjunction with the dopaminergic neuronal system.

Animals↗