Effect of naltrexone administration on short-term memory in chronically ethanol-treated outbred rats.

AIMS: The purpose of this study was to evaluate the effect of naltrexone treatment for 21 consecutive days on short-term memory in ethanol-preferring and non-preferring outbred rats. METHODS: Ethanol preferring, non-preferring and control Wistar rats were treated with naltrexone [0.1 mg/kg intraperitoneally (i.p.)] for 21 consecutive days. Short-term memory was assessed by using an olfactory social recognition test. RESULTS: A single administration of naltrexone (0.1 mg/kg i.p.) to non-ethanol-treated animals facilitated social memory, whereas the drug did not affect short-term memory in either group of chronically ethanol-treated rats. Multiple naltrexone treatment also lowered alcohol intake in ethanol-preferring rats. CONCLUSION: Naltrexone-ethanol interaction does not seem to produce any negative effect on the short-term memory in outbred rats.

Lack of ifenprodil anxiolytic activity after its multiple treatment in chronically ethanol-treated rats.

AIMS: The purpose of this study was to assess the anxiolytic activity of ifenprodil in Warsaw high-preferring (WHP) and low-preferring (WLP) rats after chronic ethanol treatment. METHODS: WHP and WLP animals, their paired-ethanol-naive groups and control Wistar rats were treated with ifenprodil (1.0 mg/kg, intraperitoneally) for 21 consecutive days. Anxiolytic activity was evaluated by using the two-compartment exploratory test. In addition, the locomotor activity paradigm was also assessed. RESULTS: Ifenprodil did not affect this paradigm in all investigated groups. The ethanol treatment led to lowering of anxiolytic scores in WHP rats. Multiple ifenprodil administration showed an anxiogenic-like activity in both WHP- and WLP-ethanol-treated groups. CONCLUSIONS: Our results suggest that, under some conditions, the role of ifenprodil in the treatment of alcoholism may be insufficient to support its use.

Ethanol facilitation of short-term memory in adult rats with a disturbed circadian cycle.

The aim of this study was to evaluate the effect of 3-month ethanol treatment on olfactory social memory test performance using two inter-exposure intervals [30 min: short-term recognition (STR); or 120 min: long-term recognition (LTR)] in adult rats with a disturbed circadian cycle (DCC). Ethanol treatment both in ethanol-preferring and -non-preferring groups improved the STR task compared to control rats. However, LTR procedure triggered the opposite tendency. Moreover, no differences between control rats with DCC and those with normal diurnal rhythm in STR and LTR paradigms were observed. Our results suggest that, under some conditions, alcohol facilitates short-term memory in adult rats.

Effects of acamprosate and scopolamine on the working memory of rats in a three-panel runway task.

The aim of this study was to evaluate the effect of treatment with single (1x) and multiple (10x) doses of the anti-craving compound acamprosate (AC, calcium acetyl homotaurinate) on working memory in rats, using in a three-panel runway test. We measured tasks after the animals were treated with AC (500 mg/kg/d, i.p.); scopolamine (SC, 0.5 mg/kg/d, i.p.), a cholinergic muscarinic receptor antagonist; or both drugs concomitantly (ACSC), either for 1 day (1x) or daily for 10 consecutive days (10x). Neither 1x not 10x AC alone had a significant effect on working memory task performance, whereas treatment with SC alone had a significantly negative effect on the ability of the rats to complete the tasks. Rats receiving ACSC performed better than those receiving SC alone, making fewer errors and displaying shorter latency, similar to the performance of the control group. These observations support the hypothesis of an indirect involvement of AC in the cholinergic system.

The effects of midazolam and morphine on analgesic and sedative activity of ketamine in rats.

The aim of this study was to investigate possible interactions between the analgesic activity of ketamine (an N-methyl-D-aspartate antagonist), midazolam (a benzodiazepine derivative) and morphine using the tail-flick test in rats. Animals were treated s.c. with ketamine (1.0-10.0 mg/kg), midazolam (0.3 mg/kg), or morphine (0.6 mg/kg) alone. or in combination The strongest analgesic effect of ketamine was observed after 3.0 mg/kg. In higher doses no enhancement of ketamine activity were found. After morphine and ketamine (3.0 mg/kg) or morphine, midazolam and ketamine co-administration. higher antinociceptive effects compared to ketamine activity were found. Rats administered midazolam and ketamine (3.0 mg/kg) showed a decrease of the effect of ketamine analgesia, and the antinociceptive effect of the three-component mixture was lower than after co-injection of morphine and ketamine. The interaction of these two compounds with ketamine (5.0 mg/kg) occurred in a different manner, because midazolam led to a strong enhancement of ketamine analgesia. After morphine and ketamine (5.0 mg/kg) administration, very weak increase of ketamine analgesia was observed. The results of this study allow better understanding of the alteration of the analgesic effects of low doses of ketamine under the influence of morphine and midazolam.

Analysis of the distribution of peripheral blood lymphocyte subsets associated with chronic ethanol treatment in rats with a disturbed circadian cycle.

The present study examined the composition of lymphoid subsets in the peripheral blood of alcohol-preferring (PRF) and non-preferring (NPF) rats, in an experimental model of alcoholism involving the disruption of the circadian cycle. The absolute and relative number of lymphocytes in specific subsets (CD3, CD4, CD8, NK, CD45RA) were measured using the flow cytometry method. When control animals with a disrupted circadian cycle (KN) were compared with a normal diurnal cycle group (KD), it was noticed that this disruption led to an increase in the absolute number of lymphocytes T (CD3(+), CD4(+) and CD8(+) cells) and lymphocytes B (CD45RA(+)). After the period of time when the alcohol preference was seen, there was a change in response - as measured by the numbers and the percentage of lymphoid subsets in NPF rats - involving a lowering of NK and CD45RA(+) cells. It seems that these animals exhibit higher sensitivity towards prolonged ethanol intoxication. However, the PRF animals - for whom the analysed values were close to those of the control group (KN) - tolerated the toxic effects of ethanol better and this may be related to their genetic predisposition.

Zolpidem involvement on memory and hypnotic effect of ethanol in chronically ethanol-treated rats.

Multiple (10x) treatment of zolpidem (1.0 or 2.0 mg/kg, orally, p.o.) led to different effects in chronically ethanol-treated and control rats. In control rats, after repeated zolpidem administration, a weaker, when compared to single administration, hypnotic effect of ethanol was observed, which may be the result of tolerance developed towards the inhibitory effect of zolpidem. However, in chronically ethanol-treated rats, the multiple zolpidem treatment led to prolongation of ethanol-induced sleep similar to the values observed in non-zolpidem-treated control animals. This suggests that zolpidem multiple administration may inhibit tolerance towards ethanol in chronically ethanol-treated rats. In the experiment with zolpidem, there were effects on performance in a memory test and the impairment of passive avoidance task after multiple drug treatment when compared to the effects after single administration in control rats. In contrast, in chronically ethanol-treated rats, amplification of latency (especially after 2.0 mg/kg) was observed. The possible relationship between ethanol-induced sedation and latency values would be consistent with a higher contribution of the inhibitory effect of zolpidem, than a direct influence on memory processes in chronically ethanol-treated rats.

The effect of chlorpromazine on pharmacokinetics and pharmacodynamics of phenobarbital in X-irradiated rats.

Male Wistar rats were irradiated with a single 600R dose of X-rays on the whole body. Chlorpromazine was given 30 min before phenobarbital. Phenobarbital sleeping time was prolonged by chlorpromazine both in irradiated and non-irradiated rats. On the 3rd day after irradiation the prolongation of the phenobarbital sleep by chlorpromazine was more marked than on the 6th day. No correlation between the pharmacodynamic action of phenobarbital and its cerebral level was noted.

Cystamine effect on the pharmacokinetics of imipramine in radiation sickness.

Investigations were carried out on the effect of cystamine premedication (100 mg/kg) before irradiation with 600 R on imipramine (40 mg/kg) kinetics in male Wistar rats. It was found that cystamine prevented changes in blood imipramine level in the irradiated animals but it protected additionally the process of drug elimination from the blood (T 1/2 beta in controls = 1.67 h, in irradiated = 2.38 h, in irradiated premedicated = 4.01 h).

Studies on the effect of cystamine on imipramine metabolism in radiation sickness.

Investigations were carried out for elucidating the effect of cystamine on the metabolism of imipramine in rats irradiated with a dose of 600 R. The investigations were based on determination of desmethylimipramine, the principal metabolite of this drug. It was found that cystamine reduced the serum imipramine level to control values but had no effect decreasing the level of desmethylimipramine. It caused also no fall in the concentration of this metabolite in brain tissue and even it raised this concentration. The authors explained these findings as a result of secondary resorption of desmethylimipramine into the blood stream, and a result of changed activity of beta-glucuronidase, these mechanisms being partly responsible for the overall effect.

Pharmacodynamics and pharmacokinetics of psycholeptic drugs in the course of radiation disease. Effect of premedication with metanabol on dynamics and kinetics of nitrazepam.

The effect of metanabol given to rats before irradiation (600 R) on exploring motility and cataleptic action of nitrazepam was investigated. The level of nitrazepam in the blood plasma and urine was determine. Most evident radioprotective effect of metanabol was found on 3rd day after irradiation. The drug inhibited the inhibited the increased response of the rats to the anticonvulsive action of nitrazepam and prevented the pharmacokinetic disturbances appearing in the course of radiation disease.

Pharmacodynamics and pharmacokinetics of psycholeptic drugs in the course of radiation disease.

The effect of metanabol (1 mg per kg) applicated to rats during 10 days before irradiation (600 R) on pharmacodynamics and some indices of thioridazine kinetics was investigated. It was found that the increased cataleptic action of thioridazine (20 mg per kg), during radiation disease was inhibited ater metanabol premedication. The protective effect of metanabol was found to be due to shortening of the half-life time of thioridazine (from 5.5 h in irradiated to 2.38 h in irradiated premedicated animals) as well as to lowering of thioridazine content in the brain tissue.

Changes in pharmacodynamics and pharmacokinetics of psycholeptic drugs in the course of radiation disease. Effects of premedication with cystamine on dynamics and kinetics of thioridazine.

Changes in pharmacodynamics and pharmacokinetics of psycholeptic drugs in the course of radiation disease. Effect of premedication with cystamine on dynamics and kinetics of thioridazine. Acta Physiol. Pol. 1977, 28 (2): 169--179. The effect of premedication with cystamine (100 mg/kg) applied before irradiation (600 R) on exploring mobility and cataleptic action of thioridazine was investigated in rats. The levels of thioridazine in blood serum, brain tissue and in bile were determined. It was found that cystamine prevents the changes in dynamics of thioridazine action in radiation disease through abolition of disturbances in kinetics of this drug. Half-life period of thioridazine was found to be reduced and its level in the brain tissue was diminished in the irradiated, cystamine-pretreated animals in comparison with the irradiated, untreated ones.

The influence of imipramine on the circulatory system and some other parameters of arterial hypertension.

Imipramine in doses of 0.35-0.45 mg/kg body weight usually induces a drop in arterial blood pressure; the drop is statistically significant in patients with essential hypertension. In these patients, a significant increase in excretion of catecholamines in urine was observed when compared with a control group. In both groups no changes in heart action were found.

The influence of cystamine on pharmacokinetics and pharmacodynamics of thioridazine.

A study on the influence of cystamine on the kinetics and dynamics of the action of thioridazine has been carried out. Higher levels of this drug in the blood and lower levels in the brain tissue than those in unpremedicated rats were determined. Half-life of thioridazine underwent shortening from 2-55 hr to 1-05 hr. Excretion of thioridazine with bile was not significantly affected by premedication with cystamine. beta-Glucuronidase activity, after an initial drop on the first day following premedication, increased to levels higher than the control values. The dynamics of the action of the thioridazine were little affected. The cataleptic action of thioridazine was enhanced on the first day after premedication with cystamine. Thioridazine depressed exploratory activity in rats more significantly only during the first three days after cystamine premedication.

Influence of cystamine on activity and biotransformation of hexobarbital.

Influence of cystamine on hypnotic potency and biotransformation of hexobarbital in rats was studied. Duration of hexobarbital-induced sleep was prolonged maximally by 42% on the first day after premedication, and by 37% on the third day. After six days, differences from the control group were within the limits of experimental error. Biotransformation of hexobarbital was only slightly inhibited in rats premedicated with cystamine, confirmed by determinations of hexobarbital oxidase activity. Excretion of hexobarbital and its metabolites was delayed.

Influence of tricyclic antidepressant drugs on experimental arterial hypertension.

The tricyclic antidepressant drugs: imipramine, opipramol, amitryptiline and nortryptiline inhibit development of experimental arterial hypertension in rats.