EtOH Injection Research Articles

Acute effect of ethanol on renal electrolyte excretion in rats

The purpose of this study was to investigate the renal handling of sodium and potassium in rats during an acute ethanol (ETOH) administration and to relate any observed changes to alterations in renin-aldosterone secretion. Eight male Wistar rats, 7 to 8 weeks of age, were injected intraperitoneally (IP) with 1.0 g/kg body wt. ETOH (15% v/v, 95% ETOH in saline, pH 6.98, osmolality 284 mOsm/kg). Blood ETOH levels were 159 ± 16 (Mean ± SEM) and 120 ± 12 mg/dl, 10 and 30 min after the ETOH injection respectively ( p<0.05). Control animals were given either an equal volume (1.77 ml/100 g body wt.) of 0.9% saline (n = 6) or 5% dextrose solution (n = 4) with similar pH and osmolality. Following ETOH administration blood pH, urine pH, plasma bicarbonate (HCO 3) concentration declined significantly ( p<0.01) while glomerular filtration rate (GFR) and hematocrit (Hct) remained unchanged ( p = 0.1). Mean fractional sodium excretion (FE Na), fractional potassium excretion (FE K), and osmolar clearance (Cosm) fell significantly despite an increase in plasma sodium ( p<0.01), potassium ( p<0.05) and osmolality concentrations ( p<0.05). There was no significant change in plasma aldosterone concentration (PA) or plasma renin activity (PRA) following the ETOH administration. No difference in GFR, FE Na, FE K, Cosm, blood pH, urine pH, plasma electrolytes, PA, or PRA was observed following the saline or dextrose injections. In conclusion, acute ETOH administration in rats alters renal sodium and potassium excretion independent of changes in GFR, PA, PRA or plasma volume as reflected by Hct.

Effects of route of administration of ethanol on high-speed reaction time in young and old rats

The blood ethanol concentrations (BECs) and reactive capacity of young (8 months) and old (24 months) male Fischer 344 rats were compared at 5, 10, 20, 45, 65, and 90 min following the administration of ethanol (EtOH). The time-dependent effects of intragastric intubation (IG; 3 g/kg) and intraperitoneal injection (IP; 1.5 g/kg) of EtOH (20% w/v) were determined. Subsequent to IG delivery, BECs rose most rapidly within the first 20 min, but did not reach peak levels until 90 min for both young (240 mg/dl) and old rats (250 mg/dl). Following IP injections, BECs escalated within 5 min to 250 mg/dl in the young, to 175 mg/dl in the old, and declined gradually to a stabilized value of 150 mg/dl (young) and 130 mg/dl (old). The old rats never achieved the high BECs seen in the young. Reactive capacity, a measure of auditory/visual reaction time, was inversely related to BECs. As BECs (IP) declined, performance improved at a similar rate in both age groups, although the old rats' performance was more impaired than that of the young. However, BEC per se was not an adequate predictor of reactive capacity. When EtOH was delivered by IG so that BECs remained high for long periods of time, reactive capacity was far less impaired compared with IP delivery in which comparable BECs were present for only a few minutes. The possibility was noted that behavioral tolerance may have developed during the 90-min post-EtOH period, and that the IP delivery method may disrupt behavior in ways independent of brain ethanol levels.

Environmental variables differentially affect ethanol-stimulated activity in selectively bred mouse lines.

Low doses of ethanol (EtOH) stimulate activity in an open field in many strains of laboratory mice. We are selectively breeding two lines of mice to exhibit a large (FAST) response on this test, and two other lines to exhibit a small (SLOW) response (Crabbe et al. 1987). The lines initially diverged in response to EtOH, but despite continued selection pressure, the difference between each pair of FAST and SLOW lines has not increased over generations as much as expected. Our practice has been to test animals on the 1st day after saline injection, and repeat the test after EtOH injection 24 h later. Lister (1987) recently demonstrated that the order in which an animal was exposed to EtOH and saline influenced the magnitude of the response to EtOH, with animals tested initially after EtOH having greater stimulation. Middaugh et al. (1987) recently demonstrated that the magnitude of EtOH stimulation was greater under conditions of relatively bright light than under dim light. Using non-selected Swiss mice, the current experiments essentially confirmed Lister's findings. Using FAST and SLOW mice, the predictions of both groups were tested. Both hypotheses were confirmed. Additionally, these experiments demonstrated that the magnitude of the difference between FAST and SLOW mice was greater under bright light than under dim light. The line difference was also greater when tested in the EtOH-Saline order. In experiments with Swiss mice, the possible role of peritoneal irritation in the EtOH effect was eliminated, and the optimal dose and time for demonstrating the effect was determined.(ABSTRACT TRUNCATED AT 250 WORDS)

Interaction between ethanol and stress on ACTH and beta-endorphin secretion.

The intraperitoneal infusion of ethanol (EtoH) (1 g/hr/kg body weight for 3 hr) to intact rats blunted the secretion of adrenocorticotropic hormone (ACTH) and beta-endorphin induced by a subsequent 10-min exposure to mild, inescapable electroshocks (1.5 mA; 2 sec; four shocks/min) or by corticotropin-releasing factor (CRF). Conversely, administration of the shocks for 3 hr diminished the pituitary response to an acute i.p. injection of EtoH. While we have previously shown (Rivier C, Vale W: Endocrinology 121:1320-1328, 1987) that prolonged stress induces a loss of pituitary responsiveness due to the depletion of pituitary ACTH stores, the infusion of EtoH did not cause statistically significant changes in pituitary ACTH content. In adrenalectomized rats, the infusion of EtoH caused an elevation of ACTH plasma levels that was significantly (p less than or equal to 0.01) larger than intact animals. These rats also showed a blunted pituitary response to the acute injection of CRF, possibly because they were already secreting ACTH at a maximal rate. These results support the hypothesis that CRF, stress, and alcohol do not potentiate each other on pituitary ACTH and beta-endorphin secretion.

Microwave attenuation of ethanol-induced hypothermia: ethanol tolerance, time course, exposure duration, and dose response studies.

Four experiments were conducted to quantify the reported attenuation by microwave (MW) irradiation of ethanol-induced hypothermia. In one experiment rats were irradiated (continuous wave 2.45 GHz, specific absorption rate = 0.3 W/kg) or sham irradiated for 45 min, injected with 3.6 g/kg, 20% (v/v) ethanol (EtOH) or saline (NaCl) i.p.. Colonic temperature was monitored at 20-min intervals for 2 h. This procedure was repeated for 8 days to determine the rate of tolerance development to the hypothermic effect of ethanol. While MW irradiation did significantly attenuate EtOH-induced hypothermia, it did not enhance or retard the rate of tolerance development. To determine the duration of irradiation necessary to attenuate EtOH-induced hypothermia, groups of rats were irradiated or sham irradiated for 5, 15, 30, or 60 min prior to EtOH injection and subsequent temperature measurements. The attenuation was apparent only after 60 min of irradiation. To determine the duration of the attenuation effect after irradiation, rats were injected with EtOH or NaCl at 0, 30, 60, 120, or 480 min after 45 min of irradiation or sham irradiation. The attenuation effect was apparent among rats injected 0 to 30 min after irradiation and for the first 40 min for groups injected at 120 min. Additional rats were injected with NaCl or 0.9, 1.8, or 2.7 g/kg of EtOH i.p. following 45 min of irradiation or sham irradiation to determine if the attenuation effect depends on the dose of EtOH administered. Attenuation of EtOH-induced hypothermia was more apparent at lower doses of EtOH than at higher doses. These results indicate that the effect is an acute response to irradiation, and rule out several other potential explanations.

Toward understanding ethanol's capacity to be reinforcing: A conditioned place preference following injections of ethanol

Rats that had previously consumed a 6% ethanol (ETOH) solution daily for 26 days and rats without such a history served as subjects in a test for the ability of ETOH to establish a conditioned place preference. The time of putative conditioning was from 4 to 8 min after injections of ETOH, 1 g/kg. The combination of programming the period of putative conditioning to be shortly after injections and using rats habituated to drinking ETOH allowed a conditioned place preference to emerge after only a few conditioning trials. Such a result potentially reveals features of the way ETOH achieves its reinforcing capability and sets the stage for understanding the mechanism of that reinforcement.

Antagonism of ethanol-evoked responses by amantadine: A possible clinical application

The behavioral and biochemical effects of amantadine hydrochloride (ATD) on some ethanol (ETOH) mediated responses in rats and mice were studied. Administration of ATD, 0.5 mM/kg, IP, prior to a narcotic dose of ETOH significantly decreased the central depressant action of ETOH, as measured by the duration of ETOH-produced narcosis in mice. The time required for the onset of ETOH-narcosis was significantly delayed in ATD-treated mice compared to controls. Analyses of whole blood and brain ETOH concentrations showed that ATD-treatment prior to ETOH significantly reduced brain content of ETOH from saline-pretreated mice at the time of onset of ETOH narcosis as well as 30 min after ETOH injection without concomitant change in blood ETOH concentrations at the respective time intervals. Administration of ATD, 0.5 mM/kg, IP, reduced voluntary intake of ETOH by rats voluntarily selecting 5% ETOH solution over water as the drinking fluid. There were no changes in cytoplasmic rat liver alcohol dehydrogenase (L-ADH) and mitochondrial aldehyde dehydrogenase (L-ALDH) activities in rats maintained on water or 5% ETOH as the drinking fluid and administered ATD, 0.5 mM/kg, IP, once or identical dose once daily for six consecutive days. However, ATD produced in vitro non-competitive inhibition of both L-ADH and L-ALDH at a concentration range between 10−3 M and 3×10−3 M assay mixture. The results indicate the potency of ATD in negating ETOH-mediated responses measured and suggest for a possible clinical trial for ATD in the management of alcoholic patients provided it is devoid of disulfiram-like reaction in man.