The histopathology of freezing injury to the rat spinal cord. A light microscope study. I. Early degenerative changes

In an effort to develop a method of tissue injury which would provide a model for the study of axonal regrowth in adult mammalian central nervous system (CNS), we have analyzed the effects of freezing in the dorsal columns of more than 200 rat spinal cords. The effects of temperature and time of exposure upon the size, shape, distribution and histologic characteristics of the lesion have been assessed during the first seven days following the injury. The upper threshold for injury occurs at -3 degrees C for 15 minutes. Between -3 degrees C and -12 degrees C the tissue changes vary in extent and characteristics. Selective damage to axons and myelin occurs with sparing of the supportive cells followed by proliferation of a cellular matrix. At seven days, the lesions produced by -8 degrees C for 15 to 60 minutes have neither axons nor myelin sheaths and consist of a dense cellular matrix of macrophages and presumed glial cells. With these tissue characteristics, and the preservation of tissue continuity without obstructive barriers, this model would appear to be potentially suitable for the study of axonal regrowth potential in mammalian CNS.     

Intracarotid hydroxyethyl methacrylate solution causing stroke in dogs

Hydroxyethyl methacrylate (HEMA) has been advocated as a polymerizing solution with which to prevent deflation of detachable balloons in interventional neuroradiology. It is pertinent to know if unpolymerized HEMA would have untoward effects if accidentally released into the carotid artery by balloon rupture or deflation. Seven mongrel dogs underwent transfemoral catheterization of the common carotid artery and subsequent injection of HEMA solution in volumes of 1 cc in five dogs, 2 cc in one, and 4 cc in one. Angiography performed at the time of injection revealed evidence of intravascular thrombosis as well as possible spasm. Three surviving animals were sacrificed at 48 hours; the brains were fixed and examined histopathologically. One brain was normal and one was autolyzed and could not be examined. Five of the seven animals had histopathologically documented cerebral infarctions of varying size. No foreign substance was seen within the blood vessels to suggest intravascular polymerization. The animals injected with 2 or 4 cc HEMA solution did not survive 48 hours. Literature review reveals little documentation of the toxicology of intravascular HEMA. With its increasing popularity as a compound for polymerization in detachable balloons introduced into the brain, further investigations are warranted to understand the physical properties of the compound and potential risks of its use.     

Effects of morphine on acquisition and maintenance of ethanol and water intake patterns in rats.

Two experiments were conducted to assess the effects of chronic subcutaneous injections of morphine (1.0 mg/kg) or saline on the pattern and amount of sweetened ethanol and water intake in fluid restricted Long-Evans rats. Following daily injections, 2-h two-bottle choice tests were conducted with water and an ethanol solution (15% ethanol v/v in 5% sucrose w/v). During a 20-day acquisition phase (Experiment 1), ethanol intake patterns and amounts did not differ between saline (n = 6) and morphine (n = 6) groups. Both groups exhibited ethanol intake patterns that decreased exponentially throughout the session suggesting control by fluid restriction procedures. Morphine decreased water intake during initial periods of each session and increased intake during later periods. In Experiment 2, morphine and saline injections were reversed across three phases with the same rats. Morphine increased total ethanol consumption during the first few days of each 15-day phase, but the groups did not differ thereafter, and the initial increases produced no statistically significant group differences. Additionally, morphine augmented ethanol intake in early portions of sessions, while water intake was decreased and increased during early and later portions of each session, respectively. Analysis of the data from the last 5 days of each phase indicated that, when injected with morphine, the group which received saline during acquisition consumed significantly more ethanol solution than the group injected with morphine during acquisition. The effect on patterns of water and ethanol intake were observed, regardless of the drug injected during acquisition.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ethanol and sucrose self-administration components: effects of drinking history.

Results of previous studies have shown that when rats consume higher concentrations of ethanol during initiation both the amount consumed and the pattern of consumption change with the return to a lower concentration. In this study, an across-sessions breakpoint procedure in the sipper-tube model was used to examine the effect that experience with drinking higher concentrations (a concentration manipulation) of both ethanol and sucrose had on appetitive and consummatory behaviors. A follow-up study was then conducted in the ethanol-consuming group with across-session breakpoint and intake examined before, during, and after a 3% sucrose/10% ethanol solution was presented in the sipper tube. As ethanol concentration increased, intake was not changed. Exposure to higher ethanol concentrations had no effect on the amount of 10% ethanol consumed when retested. The exposure tended to increase appetitive behavior (breakpoint), but this effect was not unique to ethanol, as rats self-administering 3% sucrose showed a similar increase. When the combined ethanol-sucrose solution was available, a significant increase in both intake and appetitive responding occurred; however, there was no change from prior intake or breakpoint when 10% ethanol was retested. That the addition of sucrose to the ethanol solution significantly increased appetitive and consummatory behaviors supports the suggestion that the composition of the alcoholic beverage can have a strong influence over the control of self-administration. Because most consumption of ethanol by human beings is in solutions that contain mixers that alter the taste of the solution, this taste factor needs to be considered in the regulation of ethanol drinking.     

Current possibilities for the staged rehabilitative treatment of peptic ulcer in adolescents and young adults

The authors presented the results of a follow-up of 2 groups of patients with gastroduodenal pathology diagnosed in childhood: the patients (96 persons) in the 1st group had received staged rehabilitation treatment, no staged rehabilitation measures had been used in the 2nd group (86 patients). A differentiated step-by-step complex of therapeutic and preventive measures at the onset of disease brought about positive results in 94.1% of the patients in the 1st group, whereas routine therapy without therapeutic and preventive measures at the time of remission resulted in recurrence in 72.1% (62 patients) in the 2nd group. The authors arrived at a conclusion that early detection and therapy of exacerbations of peptic ulcer and chronic ulcer-like gastroduodenitis in childhood prevented the progression of disease in young patients that was of great social importance.     

GABAergic Transmission in the Nucleus Accumbens Is Involved in the Termination of Ethanol Self-Administration in Rats

Long-Evans rats ( n = 12) were trained to lever-press on a fixed-ratio 4 schedule of reinforcement with ethanol (10% v/v) presented as the reinforcer. After implantation of bilateral stainless-steel guide cannulae aimed at the nucleus accumbens, site-specific microinjections of muscimol (1–30 ng) and bicuculline (1–10 ng) were tested for effects on ethanol-reinforced responding. Baseline response patterns were characterized by initial high rates that terminated abruptly after ∼20 min. Muscimol administration in the nucleus accumbens decreased the total number of ethanol-reinforced responses and obtained reinforcers. Bicuculline also decreased ethanol-reinforced responses and reinforcers at the highest dose tested. When a dose of bicuculline (1 ng) that was ineffective by itself was coadministered with an effective dose of muscimol (10 ng), the muscimol-induced decreases in responding were blocked. Analysis of response patterns showed that muscimol decreased ethanol self-administration by terminating responding, normally lasting 20 min, after ∼10 min with no changes in local response rate. Bicuculline decreased total responding by producing parallel, but nonsignificant, changes in time course and response rate. These data suggest that GABAergic transmission in the nucleus accumbens is involved in the termination, but not the onset or maintenance of ethanol self-administration. The specificity of this effect gives emphasis to the importance of measuring behavioral parameters, as well as products of behavior (such as intake volume) in the study of ethanol self-administration.     

Failure of a schedule-induction procedure to increase ethanol intake in an established limited-access self-administration condition.

Determining mechanisms that can increase ethanol consumption during a single drinking bout is central to understanding alcohol abuse. When rodents are used as models to study excessive drinking, most often limited and transient increases in bout size are found with various manipulations. In a variety of studies, investigators have reported that schedule-induced drinking can result in excessive consumption of either water or alcohol (ethanol) during a single drinking period in food-restricted rats. The question examined in this experiment was, Could a schedule-induction paradigm increase bout size in nondeprived rats already self-administering ethanol? After the rats were trained to self-administer a 10% (volume/volume) ethanol solution in a fixed daily drinking session, non-response-contingent presentation of a 10% (weight/volume) sucrose solution, on a fixed-time, 120-s schedule, was used to determine whether additional ethanol consumption could be induced. This was followed by the use of a fixed-time, 300-s schedule and then, by using the fixed-time, 120-s schedule, with the presentation of a 2% (weight/volume) sucrose solution. None of these conditions induced an increase in ethanol self-administration. The results indicate that factors that control ethanol bout size in the nondeprived rat are such that the standard schedule-induction condition seems to be ineffective if an ethanol bout has occurred in the recent past.     

Oral ethanol self-administration in a continuous access situation: relation to food response requirements

Rats (N = 8) were housed (23 hr/day) in a test chamber in which the presentation of food pellets and 10% ethanol were a function of a concurrent fixed-ratio schedule of reinforcement. Water was available from a drinking tube. Following a 90-day period with food pellets presented on a fixed-ratio one schedule (FR 1) and ethanol on a FR 4, the FR schedule for food presentation was systematically increased. Daily food intake declined as the FR increased up to FR 64. Decreases in food were accompanied by reduced water consumption and a three-fold increase in ethanol intake. The major increase in ethanol intake was accounted for by an increase in the number of ethanol bouts/day rather than an increase in bout size. The 24-hr cyclic pattern of food, water and ethanol ingestive behaviors found in the 90-day FR 1 period was maintained as the food presentation schedule increased. Food, ethanol, and water intake returned to the pre-FR-manipulation levels with the introduction of the food FR 1 condition. The results were discussed in terms of caloric, fluid, and activity changes resultant from the effects of the FR manipulation. No single factor could account for the increased ethanol consumption. These effects were related to previous work which demonstrates increased ethanol intake when response parameters of concurrent reinforcements are changed.