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Biomedical subjects

L Hedlund

Publications and source records attributed to L Hedlund.

At least 19 recordsLinked to original sources

Mechanisms of alcohol-nicotine interactions: alcoholics versus smokers.

This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The chairs were Toshio Narahashi and Bo Söderpalm. The presentations were (1) Nicotinic mechanisms and ethanol reinforcement: Behavioral and neurochemical studies, by Bo Söderpalm, M. Ericson, P. Olausson, and J. A. Engel; (2) Chronic nicotine and ethanol: Differential regulation in gene expression of nicotinic acetylcholine receptor subunits, by X. Zhang and A. Nordberg; (3) Nicotine-ethanol interactions at neuronal nicotinic acetylcholine receptors, by Toshio Narahashi, William Marszalec, and Gary L. Aistrup; (4) Relapse prevention in alcoholics by cigarette smoking? Treatment outcome in an observational study with acamprosate, by L.G. Schmidt, U. Kalouti, M. Smolka, and M. Soyka; and (5) Effect of nicotine on voluntary ethanol intake and development of alcohol dependence in male rats, by L. Hedlund and G. Wahlström.

Acamprosate↗

Acute and long term effects of buspirone treatments on voluntary ethanol intake in a rat model of alcoholism.

Buspirone, a 5-HT1A agonist, has been shown to decrease the intake of ethanol when given as a single dose to rats with a psychological dependence induced according to our rat model of alcoholism. The present experiment evaluates the effects different treatments with buspirone have on voluntary ethanol intake in these psychologically dependent rats. As a first treatment, buspirone was given once daily for 23 days at the dose of 20 mg/kg/day. Ethanol was withheld except for the first and the last day of the treatment. On the first day, the buspirone injection decreased ethanol intake from the pretreatment value (1.94+/-0.18 g/kg/day), down to 1.36+/-0.18 g/kg (p < 0.01, n = 12). The rats were again given a choice between water and 10% ethanol after the last injection of buspirone. During the following 24 hr period, the ethanol intake was increased to 3.56+/-0.24 g/kg/day (p < 0.001 vs. the pretreatment intake, n = 12). A loss of correlation with the pretreatment intake of ethanol indicated an altered regulation of ethanol intake for approximately 3 more weeks. Fifteen weeks after the start of the first treatment, buspirone (20 mg/kg) was re-tested as a single dose, with no effect on ethanol intake. Twenty-two weeks after the start of the first treatment, a 1-week treatment with 20 mg/kg/day of buspirone was started. During this treatment, the rats had a continuous choice between 10% ethanol and water. There was, as in the first re-test, no effect on ethanol intake on the first day of the treatment. However, on the last 2 days of the treatment, the ethanol intake was increased to 2.86+/-0.28 g/kg and to 2.89+/-0.26 g/kg respectively (p < 0.05, n = 10 on both days, compared with the pretreatment intake of 1.78+/-0.36 g/kg). Thus, an acute dose of buspirone can decrease voluntary ethanol intake in psychologically dependent rats, but long-lasting changes in the effect of buspirone seem to develop during a 3-week treatment period.

Alcohol Drinking↗

Citalopram as an inhibitor of voluntary ethanol intake in the male rat.

Psychological dependence was induced in rats by a 1-year intermittent exposure to intoxicating doses of ethanol, and recorded by the rat's ability to later take the same dose of ethanol independent of the offered concentration. Citalopram (10 or 40 mg/kg/day) was given for 3 weeks with ethanol available only the first and the last day; 10 mg/kg had no effect. On the first treatment day 40 mg/kg decreased ethanol intake. On the last treatment day 40 mg/kg had no effect. The following week the ethanol intake was higher than before the treatment in the 40 mg/kg group. During the four posttreatment weeks the ethanol intake of the 40 mg/kg group dropped significantly. Citalopram was retested 18 weeks after the first treatment during 1 week, with continuous access to ethanol; 10 mg/kg had no effect and 40 mg/kg decreased ethanol intake at day 1, reaching a minimum in day 3. A tolerance to this effect was seen at the end of the week. Thus, in this model an acute dose of citalopram can decrease ethanol intake, but tolerance to this effect develops when citalopram is given both with and without access to ethanol.

Alcoholism↗

Buspirone as an inhibitor of voluntary ethanol intake in male rats.

The effect of buspirone, a drug with mainly 5-HT1A-agonist activity, on voluntary ethanol intake was tested in a rat model of alcoholism. In this model the treatment consists of an injection of ethanol (2.0 g/kg) or saline once a week, preceded by a 24 h choice between water and ethanol (10% w/v). This weekly injection of ethanol reduces voluntary ethanol intake in male rats. Maximal inhibition is seen after 5-6 weeks. At this maximal inhibition buspirone or saline was injected prior to the voluntary 24 h intake of ethanol in both the ethanol- and saline-injected groups. The tested doses were 5 mg/kg (week 5) and 20 mg/kg (week 6). There was no reduction in ethanol intake in the buspirone-injected groups when compared with their corresponding controls. A second experiment with buspirone was performed during the evaluation period following treatment with ethanol. This treatment consisted of a choice between water and ethanol (10%, w/v) for 1 day each week, followed by an injection of ethanol 2.0 g/kg) and lasted for 52 weeks. During the evaluation period the rats had a continuous choice between ethanol and water for 37 weeks and no injections were given. In this situation, with a longer exposure to ethanol, a dose of 20 mg/kg of buspirone in week 90 reduced ethanol intake by approximately 40%, when compared with controls. The effect of this buspirone dose lasted at least a week. This indicates that the long-term exposure to ethanol in the second experiment induces changes that affect the serotonergic transmission, and that this changed neural system is involved in the regulation of voluntary ethanol intake.

Alcohol Drinking↗

Diffusion/microcirculation MRI in the rat brain.

The CO2 fraction of an anesthetized rat's breathing mixture was changed (from 0 to 10%) to attempt to change the brain microcirculation and observe these changes in diffusion measurements of the neural tissue. Brain apparent diffusion coefficients were measured to be (0.71 +/- 0.01) X 10(-3) mm2/s before sacrifice and (0.39 +/- 0.01) X 10(-3) mm2/s after sacrifice. Multiple diffusion components were observed, consistent with flowing material, but the extra components did not increase with increased CO2. It is proposed that the additional components may be due to extracellular, extravascular water such as CSF.

Animals↗

Pulmonary angiography with iopamidol and Renografin 76 in normal and pulmonary hypertensive dogs.

The cardiovascular response produced during pulmonary angiography performed with the standard ionic agent diatrizoate (Renografin 76) and a new non-ionic agent iopamidol was compared. Nine dogs were evaluated while ventilated on room air and on 10% O2 which significantly elevated pulmonary arterial pressure. Iopamidol produced similar changes in mean aortic and pulmonary arterial pressures compared with normal saline (less than 20% change). Renografin 76, however, produced a significantly greater elevation in mean pulmonary arterial pressure (a 41% increase) and depression in mean aortic pressure (a 40% reduction) than either saline or iopamidol (p less than 0.01). These results were similar for dogs being ventilated with room air and oxygen. The results indicate that iopamidol should be better tolerated and therefore a safer contrast agent for pulmonary angiography than diatrizoate.

Animals↗

Nonradioactive iodoantipyrine enhanced cranial computed tomography: preliminary observations.

Nonradioactive 4-iodoantipyrine, an iodinated indicator that freely diffuses across the blood-brain barrier, was serially imaged in vivo using computed tomography (CT). Prominent enhancement was immediately detected in the brain substance of the dog following the intracarotid injection of this contrast medium. An estimate was made of the brain:blood partition coefficient for 4-iodoantipyrine from the CT derived arterial and brain concentration of this iodinated marker. Practical applicability of this technique is limited unless an improved method for getting the 4-iodoantipyrine into solution can be developed. However, this study reinforces the concept that local cerebral blood flow and metabolism can be analyzed by diffusible tracers using CT.

Animals↗

Melatonin: daily cycle in plasma and cerebrospinal fluid of calves.

Melatonin was measured by radioimmunoassay in jugular vein plasma and lateral ventricle cerebrospinal fluid collected from calves at 12 times of the day and night. Melatonin in cerebrospinal fluid increased 17-fold from an average (+/- standard error) of 38 +/- 8 picograms per milliliter during the day to an average of 637 +/- 133 picograms per milliliter during the night (P less than .001). Plasma concentrations of melatonin increased sixfold from an average, per milliliter, of 19 +/- 4 picograms during the day to 121 +/- 24 picograms during the night (P less than .001).

Animals↗

Cerebral ventricle cannulation in the calf.

A stereotaxic apparatus and procedure for surgically implanting guide cannulae for access to the cerebral ventricles of the calf are described. This type of implant permits chronic ventricular injections and collections of mililiter quantities of cerebrospinal fluid from the nonanesthetized calf.

Anesthesia, Inhalation↗

Behavior of lactating dairy cows during total confinement.

Daytime activity of four lactating Holstein cows housed in total confinement in stanchion stalls for about 14 wk was observed continuously, and activities such as eating, drinking, resting, ruminating, and socializing were recorded. Observations were by closed-circuit television and a switch panel connected to an event recorder. During the 15 h of daytime, the cows spent an average of 45% of the time lying, 26% eating, 22% ruminating, 1% drinking, and 2% socializing. Most eating occurred during standing (98.4%) while most rumination occurred during lying (59%). The distribution of these activities by time of day was similar to that of pastured dairy cows. Periods of eating, drinking, and social activity were most intense during and shortly after the morning and afternoon milking and feeding times. Conversely, periods of greatest recumbency, rumination, and rest occurred between feeding time from midday to late afternoon. Thus, in spite of prolonged total confinement, the four cows continued to exhibit behavioral activities (duration and distribution) which are typical of less confined cattle.

Animals↗

Peripheral sympathetic innervation of the deep pineal gland of the golden hamster.

Both the superficial and deep pineal components of the intact hamster contain a rich network of green to yellow-green fluorescent nerve fibres. After either superior cervical ganglionectomy or after transection of the nervi conarii the majority of the fluorescing fibres disappeared from both the superficial and deep pineal masses. Although the deep pineal remained intact after surgical removal of the superficial pineal, it was devoid of any green or yellow-green fluorescent fibres.

Animals↗

Pineal function and oviposition in Japanese quail: superior cervical ganglionectomy and photoperiod.

Bilateral ablation of the superior cervical ganglia appears to deprive the pineal body of sympathetic innervation. Although this procedure presumably interrupts the neural circuit for transmission of optic information to the pineal, oviposition rates of ganglionectomized females exposed to stimulatory (15-hour) or to nonstimulatory (4-hour) daily photoperiods do not differ from those of the controls.

Animals↗