Ethanol effects on female aggression vary with opponent size and time within session

Female rats displayed different patterns of attack to large and small male intruders into their home cages, as a function of ethanol dose levels. In confrontations with small male intruders, female attack increased significantly at 0.3 g/kg ethanol, declining to saline levels with higher doses (0.6 and 1.2 g/kg). Attack toward large intruders was (nonsignificantly) higher at 0.3 g/kg ethanol, and declined to significantly lower than saline levels with the higher ethanol doses. The attack increases seen with low ethanol doses came in the initial 5-min block of the 30 min test session, and did not persist. These findings suggest that low ethanol doses may especially increase overt aggression in situations in which the tendency to attack is only moderately inhibited by factors such as opponent size or the potential danger of retaliatory attack.     

Ethanol induces conditioned place preference in genetically selected alcohol-preferring rats

The study of the biological mechanisms of ethanol reward has greatly suffered from problems to obtain ethanol-induced conditioned place preference (CPP) in rats. In the present study, CPP was obtained in genetically selected Marchigian Sardinian alcohol-preferring (msP) rats, derived from Sardinian alcohol-preferring rats, following intragastric (IG) ethanol administration by means of a permanent IG catheter, but not after intraperitoneal (IP) injection or IG gavage. Rats with permanent IG catheter, received IG administration of 0.35, 0.7, 1.5 or 2.8 g/kg ethanol, as a 10% v/v solution. In ethanol-experienced rats 0.7 or 1.5, but not 0.35 or 2.8 g/kg ethanol significantly increased in comparison to controls the time spent in the ethanol-associated previously non-preferred compartment, which became preferred in the post-conditioning test. In ethanol-naive rats, only 0.7 g/kg ethanol significantly increased the time spent in the ethanol-associated compartment. On the other hand, no effect was observed in alcohol-experienced rats following IG gavage, or IP injection of 0.35, 0.7 or 1.5 g/kg ethanol. The present results provide evidence that ethanol possesses postingestive rewarding properties in msP rats, and that it can reliably induce CPP in them, provided that an appropriate method of administration is adopted. Received: 26 October 1997/Final version: 26 May 1998     

Ethanol enhances Nicotine's effects on DRL performance in rats

The present experiment examined effects of nicotine (0.0, 0.3, 0.56, and 1.0 mg/kg; IP) and ethanol (0.0, 0.5, 1.5, and 3.0 g/kg; IG) on operant behavior using a differential reinforcement of low response rate (DRL) schedule in rats. DRL schedules are sensitive to effects of nicotine and provide an assessment of the subject's ability to accurately estimate time and to inhibit schedule-controlled responding. When administered alone, nicotine shifted the mode of the interresponse time distribution to the left and reduced the percentage of reinforced responses. Nicotine also had an inverted U-shaped dose effect on the number of "bursting" responses. When administered after pretreatment with ethanol, nicotine's effects on the distribution of interresponse times and bursting were potentiated. These effects are consistent with previous reports and with the suggestion that ethanol pretreatment can potentiate effects of subsequently administered nicotine. Published by Elsevier Science Inc.     

Behavior, adrenocortical activity, and brain monoamines in Norway rats selected for reduced aggressiveness towards man

Wild Norway rats were selected over 20 generations for reduced aggressiveness towards man. Selection for this characteristic was accompanied by many physiological changes. Although neophobia was significantly inhibited, and irritable aggression reduced by selection, no changes were revealed in mouse-killing behavior or in intermale aggression. The mean level of 5-hydroxyindole acetic acid in the hypothalamus as well as serotonin (5-HT) content in the hypothalamus, the midbrain and the cortices was higher in the 'domesticated' than in aggressive rats. Mean hypothalamic norepinephrine (NE) level also tended to be higher in the 'domesticated' animals. The resting corticosterone level and the response of the hypothalamic-pituitary-adrenocortical axis to an emotional stressor or intracerebroventricularly administered 5-HT or NE were decreased in domesticated rats compared to their aggressive counterparts. It is suggested that the diminution of the hypothalamic-pituitary-adrenocortical function as a result of selection for domesticated types of behavior depends, at least partly, on changes in brain monoaminergic systems.     

Attentional effects of nicotine and amphetamine in rats at different levels of motivation

Rationale The effects of drugs on performance of tasks used to assess attention might be confounded with changes in motivation. Few studies have investigated the role of motivational factors in such situations.Objectives To determine how changes in motivation for food influence performance of the 5-choice serial reaction time task and whether the effects of nicotine and amphetamine can be explained by motivational changes.Methods Male hooded Lister rats were trained to respond to a 1-s light stimulus presented randomly in one of five apertures in order to obtain food reinforcers. For three groups of rats (n=9–10), access to food was restricted to maintain body weights at 80, 90 or 95% of control weights. Saline and nicotine (0.025–0.2 mg/kg) were tested in each group, with and without pre-feeding (5 g). In a second experiment, saline and amphetamine (0.03–0.9 mg/kg s.c.) were tested without pre-feeding.Results High levels of motivation for food were associated with increases in anticipatory responses, fewer omission errors, shorter response latencies and completion of more trials, without change in accuracy. Nicotine, but not amphetamine, increased accuracy and the number of trials completed; whereas amphetamine, but not nicotine, increased omission errors. Both drugs decreased anticipatory responding at the largest doses tested. There were few interactions of motivational level with drug effects.Conclusions The improvements in performance produced by nicotine did not resemble the effect of increased motivation, but some effects of amphetamine resembled those of reducing the level of motivation for food. Motivational levels did not confound assessments of the attentional effects of the drugs in terms of response accuracy.     

Differential effects of electroconvulsive shock on four models of experimentally-induced aggression in rats

The effects of electroconvulsive shock (ECS) on the hyperemotionality and muricide in olfactory bulbectomized rats (OB rat) were compared with those in spontaneous killer rats (SP rat), raphe lesioned rats (Raphe rat) and delta 9-tetrahydrocannabinol treated rats (THC rat). Single and chronic treatment of ECS inhibited the muricide and attack response to a rod, but did not affect the struggle response to handling and flight response to air blowing. Muricide was markedly inhibited by ECS in OB and SP rats, and was moderately inhibited in THC rats, while it was slightly inhibited in Raphe rats. The present result indicates that muricide of OB rats is a useful model for evaluating antidepressant drugs as this behavior is markedly inhibited by ECS in OB rats. Furthermore, it is suggested that the effect of ECS on muricide is different depending upon the methods to induce muricide, although muricide itself seems to be behaviorally similar.     

Ethopharmacological studies differentiate the effects of various serotonergic compounds on aggression in rats

A series of experiments was performed to investigate the effects on aggression of various drugs affecting serotonergic transmission in rats. Using ethologically derived behavioural categories, the behaviour of treated animals was described. Drug effects were observed in two aggression models: resident–intruder aggression (RI) in male rats, and maternal aggression in lactating females during the postpartum period (MA). The 5-HT_1A agonists, buspirone, iosapirone, and 8-OH-DPAT, decreased aggression in RI and MA but simultaneously led to a marked decrease in social interest and activity, indicative of a nonspecific anti-aggressive profile. Nonselective 5-HT agonists, such as RU 24969, eltoprazine (DU 28853), and TEMPP, reduced aggression quite specifically and did not decrease social interest or exploration, but sometimes even increased these behaviours. In RI and MA, the behavioural effects of these drugs were roughly similar. By contrast, MA was more sensitive to the treatment with the 5-HT reuptake blocker fluvoxamine, which blocked RI aggression only nonspecifically at the highest dose. DOI, a 5-HT₂ and 5-HT_1C agonist, decreased aggressive behaviour and increased inactivity, without affecting social interest and exploration in RI as well as MA. This was, however, accompanied by “wet dog shaking,” characteristic of 5-HT₂-receptor stimulation. The nonspecific 5-HT agonist (and 5-HT₃ antagonist) quipazine also induced “wet dog shaking” at doses that suppressed aggression, social interest and exploration but increased inactive behaviours (sitting and lying). The discussion attempts to delineate a role for 5-HT receptor subtype involvement in the modulation of aggression, with the restrictions we clearly face with regard to the lack of specific serotonergic agonists and antagonists for certain receptor subtypes. By and large, male and female rats react similarly to treatment with serotonergic drugs stressing the consistent role of 5-HT in different forms of aggression. © 1992 wiley-Liss, Inc.     

Acute effects of AMPA-type glutamate receptor antagonists on intermale social behavior in two mouse lines bidirectionally selected for offensive aggression

Involvement of AMPA-type glutamate receptors in the regulation of social behavior has been suggested by experiments with mice deficient for the GluR-A subunit-containing AMPA receptors showing reduced intermale aggression. In the present study, effects of AMPA receptor antagonists on mouse social behavior towards unfamiliar Swiss-Webster males on a neutral territory were tested using male subjects from the Turku Aggressive (TA) and Turku Non-Aggressive (TNA) mouse lines bidirectionally selected for high and low levels of offensive aggression. The drugs were the competitive antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and 2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide (NBQX), and the non-competitive antagonist 4-(8-methyl-9H-1,3-dioxolo[4,5-h][2,3]benzodiazepin-5-yl)-benzenamine (GYKI 52466). In TA mice, CNQX and NBQX decreased the biting component of aggressive structure, while GYKI 52466 suppressed all aggressive manifestations. All drugs increased anxiety-like behavior towards the partner. In TNA mice, NBQX activated mouse social behavior and ambivalent aggression, while CNQX and GYKI 52466 only increased anxiety. Thus, AMPA receptor antagonists affect aggressive behaviors in TA mice supporting the idea that AMPA receptors are involved in the modulation of agonistic impulsive behavioral pattern. GYKI 52466 appeared to be the most selective and efficacious in suppressing the aggression.     

The effects of selected antidepressant drugs on timing behaviour in rats

It has been suggested that the increased reinforcement rate on a differential-reinforcement-of-low-rate of responding (DRL) schedule observed following acute antidepressant administration in the rat is due to an improvement in timing accuracy. The aim of the present work was to evaluate the effects of antidepressants in another schedule that requires accurate estimation of time intervals, the peak procedure. Three antidepressant drugs were tested, the tricyclic antidepressant imipramine (1.0–10.0 mg/kg, IP) and the 5-HT reuptake inhibitors, zimelidine (10.0–40.0mg/kg, IP) and clomipramine (1.0–10.0 mg/kg, IP). For reference, the full benzodiazepine receptor agonist, diazepam (1.0–5.0 mg/kg, IP) and the psychomotor stimulant, d-amphetamine (0.5–1.5 mg/kg, SC) were also tested. All doses of d-amphetamine tested significantly increased lever-pressing rates, whereas all the other compounds induced significant decreases in lever-pressing rates. Overall, the time at which the maximal lever-pressing rate occurred was not altered by any of the compounds, suggesting that timing accuracy was not significantly affected by any of the compounds administered. The only exception was zimelidine (40.0 mg/kg), which reduced the time at which the maximal lever-pressing rate occurred, although lever-pressing rates were also significantly reduced at this dose. These data suggest that previously reported antidepressant-induced improvement in performance on the DRL schedule may not have been due to improved timing accuracy per se but may have been due to a decrease in lever-pressing rates. Received: 5 December 1996/Final version: 17 June 1997     

Influence of different types of stress on selected cardiovascular parameters in rats

Wistar strain male albino rats were exposed to different types of stressors like isolation, immobilization, overcrowding and forced swimming, for a duration of one day, 7 days, 15 days and 30 days and the effect on heart weight, adrenal weight, heart rate, P-R interval and serum transaminase levels were studied. There was a significant increase in the heart weight and adrenal weight in most of the stress subgroups. Tachycardia was seen in all the types of stress upto 7 days, except in the case of overcrowding stress. Serum transaminase level increased significantly in all the types of stress. Among the different types of stress, immobilization and forced swimming had greater effect on the heart weight and heart rate. Increase in the heart rate and heart weight was observed only in the initial period of exposure to a stressor and when the animals were exposed to a prolonged stressor like 15 days and 30 days, there was no further increase in the heart weight and heart rate which may be due to the adaptation of the animal to a chronic stressor.     

Ethanol effect on acid resistance of selected enteric polymers

The aim of this study was to investigate under in vitro conditions the influence of ethanol on acid resistance of four commercially-available enteric polymers (Acryl-EZE^®, AQOAT^®, Hypromellose phthalate, and Sureteric^®). For this purpose, custom-prepared paracetamol tablets were coated with the enteric polymers and tested for release using the buffer-addition method. Ten different hydro-ethanolic media were used in the acid stage corresponding to five levels of ethanol (0, 5, 10, 20, and 40% v/v) in two acidic solutions representing low and high gastric pH (0.1?N HCl pH 1.2, L_GpH, and phosphate buffer pH 4.0, H_GpH, respectively). The coats were found to resist both types of acidic solution with ethanol percentages up to 10% leading to release profiles that conformed with the pharmacopeial requirements (<10% release after 2?h in acid stage) except for Acryl-EZE^®, which showed a premature release in H_GpH media. At the higher ethanol levels (20 and 40%), premature release associated with increased acid uptake by coated tablets was noticed for all polymers and more remarkably in H_GpH media. ANOVA tests revealed significant effects of polymer type, acidic solution type, and ethanol level on the onset and extent of premature release.     

Ethanol does not affect discriminative-stimulus effects of nicotine in rats

The effects of ethanol were evaluated in rats trained to discriminate 0.4 mg/kg of nicotine from saline under a fixed-ratio 10 schedule of food delivery. Ethanol (0.1-1 g/kg, i.p.) did not produce any nicotine-like discriminative effects and did not produce any shift in the dose-response curve for nicotine discrimination. Thus, the ability to discriminate nicotine's effects does not appear to be altered by ethanol administration. However, the high dose of 1 g/kg ethanol, given either alone or in combination with nicotine, markedly depressed food-maintained responding. This later effect was associated in some rats with an attenuation of the discriminative-stimulus effects of the training dose of nicotine. This suggests that previous reports of increased tobacco smoking following ethanol consumption in humans are connected, in some way, with an increase in motivation to consume nicotine that is produced by ethanol, rather than with a decrease in the subjective response to nicotine.     

Differential effects of chronic ethanol on apomorphine-induced locomotion, climbing and aggression in rats

Male Wistar rats were tested for apomorphine-induced locomotion, climbing and aggression after 3 week's intragastric ethanol (EtOH) treatment, 5 g/kg as 20% solution daily. The ability of apomorphine (APO) to elicit rearing (1 mg/kg i.p.) and climbing (0.5 mg/kg i.p.) was significantly suppressed in EtOH withdrawn animals. General locomotor activity in response to 1 mg/kg of APO i.p. did not differ between control and EtOH-treated groups. Affective aggression was checked in pairs of low-aggressive rats, i.e. resistant to the aggression inducing action of 10 mg/kg APO. No symptoms of aggression appeared in control animals whereas EtOH administered rats responded with marked aggression to APO. The different effect of chronic EtOH on responsiveness to APO in three behavioral models is discussed in terms of varying involvement of dopaminergic systems and receptors in behavioral phenomena as well as their susceptibility to prolonged EtOH.     

Chronic administration of aluminium L-glutamate in young mature rats: effects on iron levels and lipid peroxidation in selected brain areas

Clinical and experimental studies have demonstrated the neurotoxicity of aluminium (Al), notably as a result of lipid peroxidation in vitro. We previously showed that Al is able to cross the blood-brain barrier as an L-glutamate complex and be deposited in rat brain. The present work in young mature rats investigated the in vivo effects of chronic Al-L-glutamate treatment on Al and iron movement in plasma and selected brain regions. Brain lipid peroxidation was determined by evaluating the production of thiobarbituric acid reactive substances (TBARS) and analysing polyunsaturated fatty acids (PUFAs) such as C20:4n-6 and C22:6n-3. Our results indicate that iron concentration was decreased in plasma and that Al accumulated especially in striatum where iron levels were decreased and in the hippocampus where TBARS were increased without PUFA modifications. These data show that Al administered chronically as an L-glutamate complex is neurotoxic in vivo and thus provides a good model for studying Al toxic mechanisms.     

Antisecretory and anti-ulcer effects of morphine in rats after gastric mucosal aggression

The effects of morphine on gastric secretion, barrier mucus and mucosal lesions were studied in pylorus-ligated rats treated with the ulcerogenic agents, indomethacin, aspirin or taurocholic acid. All three ulcerogenic agents induced significant mucosal lesions. Morphine decreased gastric acid secretion and suppressed the aspirin- and taurocholic acid-induced, but not the indomethacin-induced mucosal lesions. These results suggest that the ulcerogenic mechanisms of indomethacin and the other agents are not identical. Moreover the antiulcer effect of morphine appears to be mediated by an increased barrier mucus level: the amount of Alcian blue bound to the mucosa, an indirect estimate of the adherent mucus layer, was increased by morphine and correlated with its protective effect. All morphine effects were reversed by naloxone.     

Flunitrazepam in combination with alcohol engenders high levels of aggression in mice and rats

Rationale

Higher doses of benzodiazepines and alcohol induce sedation and sleep; however, in low to moderate doses these drugs can increase aggressive behavior.

Objectives

To assess firstly the effects of ethanol, secondly the effects of flunitrazepam, a so-called club drug, and thirdly the effects of flunitrazepam plus alcohol on aggression in mice and rats.

Methods

Exhaustive behavioral records of confrontations between a male resident and a male intruder were obtained twice a week, using CF-1 mice and Wistar rats. The salient aggressive and non-aggressive elements in the resident's repertoire were analyzed. Initially, the effects of ethanol (1.0 g/kg), and secondly flunitrazepam (0; 0.01; 0.1; and 0.3 mg/kg) were determined in all mice and rats; subsequently, flunitrazepam or vehicle, given intraperitoneally (0; 0.01; 0.1; and 0.3 mg/kg) was administered plus ethanol 1.0 g/kg or vehicle via gavage.

Results

The most significant finding is the escalation of aggression after a moderate dose of ethanol, and a low dose of flunitrazepam. The largest increase in aggressive behavior occurred after combined flunitrazepam plus ethanol treatment in mice and rats.

Conclusions

Ethanol can heighten aggressive behavior and flunitrazepam further increases this effect in male mice and rats.     

Differential effects of ethanol on plasma catecholamine levels in rats

Acute ethanol administration (1-4 g/kg, i.p.) had no effect on plasma catecholamine levels in nonstressed animals except at the highest dose where levels of both catecholamines increased. In animals stressed for 30 min, the higher doses had a biphasic effect on plasma catecholamines; at earlier times during stress a reduction in stress-induced increases in both catecholamines was seen, whereas later during stress or after release from stress an increase was noted. Semi-chronic ethanol administration (0.5 and 2 g/kg/day, i.p.) had no significant effect on plasma catecholamine levels in nonstressed rats. In stressed rats, ethanol reduced stress-induced catecholamine increases but these reductions were less than those seen after acute administration. Although ethanol reduced the gross behavioral stress response, no correlation between gross behavioral and biochemical responses was detected. These data show that ethanol can indeed reduce the behavioral and biochemical stress responses in rats but that effects seen depend on the state (nonstressed vs stressed) of the animal, the dose of ethanol (low vs high) used, the length of ethanol administration (acute vs semi-chronic), and the time of measurement of the catecholamine level after ethanol administration.