Shock-induced Fighting Research Articles

Instrumental REM sleep deprivation in neonates leads to adult depression-like behaviors in rats.

Previous studies have demonstrated that neonatal suppression of rapid eye movement (REM) sleep by pharmacologic agents, particularly clomipramine, produces adult depressive behavior. These findings suggest the hypothesis that REM sleep deprivation (RSD) mediates the depressogenic behaviors of neonatally administered antidepressant drugs. Drug suppression of RSD, however, was thought to be confounded by the other effects of the drugs. The current study was aimed to show the adult effect of neonatal RSD in rats by instrumental means, ie, a computer-controlled shaking method. Three treatment groups were studied: an instrumental RSD group, a yoked control group, and a nonshaken, maternally separated, control group. All treatments began at the age of 14 days and lasted for 7 days. Adult behavior measurements including tests of sexual activity, locomotor activity, shock-induced fighting, and sleep recording were subsequently performed. The major findings of our investigation were that rats subjected to neonatal instrumental RSD demonstrated diminished sexual activity, decreased aggressive behavior, increased percentage of REM sleep, and decreased wake-REM sleep ratio compared with yoked control rats. These data are compatible with the findings from adult rats subjected to neonatal treatment with the REM-sleep suppressant, clomipramine, and supports the hypothesis that neonatal RSD results in adult depressive abnormalities. Neonatal RSD induced by a nondrug method results in adult depression-like changes similar to those induced by a REM-sleep suppressant drug, although the extent of these changes varies.

Effect of 5-{3-[((2S)-l,4-Benzodioxan-2-ylmethyl)amino]propoxy}-1,3-benzodioxole HCl (MKC-242), a Novel 5-HT1A-Receptor Agonist, on Aggressive Behavior and Marble Burying Behavior in Mice

Behavioral effects of 5-{3-[((2S)-l,4-benzodioxan-2-ylmethyl)amino]propoxy}-l,3-benzodioxole HC1 (MKC-242), a novel 5-HT1A-receptor agonist, were evaluated using animal models of anxiety and obsessive compulsive disorder and compared against reference compounds. MKC-242 suppressed foot shock-induced fighting behavior without loss of motor coordination in mice as the reference compounds did. The ED50 values of MKC-242, buspirone, tandospirone and diazepam were 1.7, 42, 80 and 2.0 mg/kg, p.o., respectively. The duration of the suppression of fighting by MKC-242 was longer than those of buspirone and tandospirone and comparable to that of diazepam. Similar results were also obtained with the water-lick conflict test in rats. The plasma concentration of MKC-242 in rats was much higher than the reported value of buspirone during 0.25-6 hr after oral administration. In addition, MKC-242 reduced marble burying behavior without reduction of motor activity. Fluoxetine, tandospirone and diazepam also reduced the behavior at non-sedative doses. These findings indicate that MKC-242 possesses a longer-lasting anxiolytic effect than azapirones. This might be due to the high concentration of the compound in plasma. In addition, it is also suggested that MKC-242 possesses an antiobsessional effect.

Effects of alcohol dependence on shock-induced fighting: Action of muscimol and homotaurine

We have applied the electroshock-induced fighting behavior to the study of experimental alcohol dependence. Adult Wistar rats were intoxicated chronically with ethanol (10 g/kg/24 h) for 13 days. Electroshock-induced fighting behavior was studied during chronic intoxication and withdrawal in comparison with normal rats receiving a water-carbohydrate solution isocaloric to ethanol. Rats were divided into groups receiving respectively muscimol (0.25 mg/kg), a GABAA agonist; homotaurine (140 mg/kg) a GABA mimetic; and physiological saline (10 ml/kg), intraperitoneally. During chronic intoxication, rats showed an increase in defensive-fighting behavior. Withdrawal accentuated the aggressive behavior and muscimol and homotaurine inhibited it. These results confirm the relevance of the electroshock-induced defensive fighting behavior test in chronic intoxication with alcohol, but to show the involvement of GABAergic transmission in the behavioral effects of alcohol withdrawal, additional experiments with other GABA mimetics and with GABA antagonists should be considered.

Pharmacological and Behavioral Profile of Alpidem as an Anxiolytic

Pharmacological and behavioral studies in mice and rats have shown that the imidazopyridine alpidem possesses anxiolytic activity with a profile which is substantially different from that of benzodiazepines. Thus, in mice, alpidem inhibited marble-burying behavior and enhanced feeding under stressful conditions, as did benzodiazepines; in contrast to these drugs, however, alpidem was inactive against shock-induced fighting and shock-suppressed exploration. In rats, alpidem exerted anticonflict activity in the punished drinking test, but failed to antagonize punishment-induced inhibition of operant behavior. Moreover, in rats trained to discriminate chlordiazepoxide from saline, alpidem did not produce a benzodiazepine-like interoceptive stimulus. Alpidem also produced anticonvulsant effects in a variety of tests sensitive to benzodiazepines. However, the order of potencies against convulsions induced by different convulsive agents was different from that of the benzodiazepines. Alpidem decreased motor performance in the rotarod test and only produced a deficit in muscle strength at doses which were more than 20 times higher than the doses active in anxiolytic tests. Moreover, alpidem did not interfere with the acquisition of conditioned fear, except at very high doses, indicating a weak potential to impair memory. The effects of alpidem were antagonized by flumazenil, indicating that central omega receptors are involved in the action of this drug. The weak sedative effects of alpidem may be attributed to its low intrinsic activity, as demonstrated by its low efficacy in increasing latency to isoniazid-induced convulsions.

Enhanced Affective Aggression in Genetically Bred Hypercholinergic Rats

Affective aggression was studied in pairs of Flinders Sensitive Line hypercholinergic rats (FSL) and Flinders Resistant Line (FRL) rats in shock-induced and apomorphine-induced fighting tests. FSL rats were significantly more aggressive in both tests. They had higher pain threshold, assessed by the jump-flinch method, than FRL rats. It is concluded that genetically developed cholinergic system supersensitivity has resulted in enhanced responsiveness to stimuli eliciting affective aggression.

Pain-induced aggression: An ethological perspective

Pain-induced aggression has been studied mainly in animals, but generalizations are made to human aggression, noteably in Berkowitz’s “aversive-stimulation” view. This review reevaluates the motivational basis of pain-induced attack by considering it from an ethological perspective. Studies supporting the view that shock-induced attack is fear-motivated are briefly reviewed before consideration of evidence that does not support this view, from naturally-ocurring examples of pain-induced attack, and from examples of sex and hormonal effects. A reconcilliation between the apparently conflicting views is suggested by distinguishing between the functional (competitive-protective) dimension and the causal (offensive-defensive) dimension. It is proposed that pain-induced attack is protective in function but can be offensive or defensive (or both) in its form; the offensive form is only rarely observed under laboratory conditions. The implications of this view are discussed (1) for the use of shock-induced fighting as an animal model of aggression; and (2) for studies of human pain-induced aggression. Ethical issues surrounding shock-induced aggression research are considered.

Spontaneously hypertensive wistar-derived male rats are more aggressive than those of their normotensive progenitor strain

We compared a group of spontaneously hypertensive rats (SHRs) to a group of Wistar-Kyoto (WKY) rats on each of the three most commonly studied forms of aggressive behavior in rats: muricide, intraspecific aggression, and shock-induced fighting (SIF). A significantly higher proportion of SHRs were muricidal; they also fought more at the lowest shock level. A trend for a higher incidence of intraspecific offense behaviors by SHRs was not significant. SHR flinch and jump thresholds were lower than the respective WKY thresholds. Although there were no significant correlations between shock thresholds and any aspects of SIF, the possibility that strain differences in shock sensitivity may contribute to differences in SIF cannot be ruled out. Within strains, there were no correlations among the different forms of aggression. Several different inherited characteristics may be associated with the accentuation of different forms of aggression in SHRs.

Animal depression model by neonatal clomipramine: Reduction of shock induced aggression

Clomipramine, administered to neonatal rats, has been reported to produce adult behavioral and REM sleep abnormalities. They include decreased sexual behavior, increased ambulation in the outer part of an open-field arena, increased REM sleep % of total sleep time, and in descriptive data, short REM latency, and increased REM phasic events. Since these abnormalities resemble some found in human endogenous depression, we have hypothesized that the adult rats represent an animal model of depression. Diminished aggressive behavior is a common characteristic of endogenous depression. This study tested the validity of the animal depression model by determining in rats the effect of neonatal clomipramine on adult shock-induced fighting. Experimental rats were treated neonatally with clomipramine and control rats were treated neonatally with saline. When they matured, compared with control rats, experimental rats had significantly fewer offensive fighting responses, and significantly more defensive fighting responses. The findings add some support to the validity of the animal depression model produced by neonatal clomipramine.

Differential influences of different stressors upon midbrain raphe neurons in rats

Various types of stressors were given to different groups of animals to examine their effects on the mesostriatal and mesolimbic serotonergic pathways. Results indicate that shock-induced fighting experience preferentially decreased serotonin (5-HT) levels in the dorsal raphe and striatum, while air puff stimulation selectively lowered 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) contents in the median raphe and hippocampus. Both immobilization and light footshock stress have a more consistent effect on both serotonergic systems. These results suggest that different stressors have differential influences upon central 5-HT neurons and, other than anatomical differentiation, these serotonergic neurons are not homogeneous with respect to their responses to stress either.

Opioids and Motivation

Emotions, experienced subjectively, appear enigmatic and inaccessible to scientific analysis, but affect many concrete psychological phenomena, such as pain sensitivity and reactions to every-day experiences. Recent evidence suggests that opioid peptides, in particular β-endorphin, may influence motivational processes by affecting emotions. Opioid peptides are found in the nervous system and peripheral tissues and produce effects similar to those of opioid drugs. β-Endorphin, whose action has a long duration, may function as a hormone and as a neuromodulator, rather than as a classical neurotransmitter. It is released by stress and causes hyperthermia and an increase in threshold pain. Endogenous opioids also stimulate food and water intake. Biochemical and behavioural experiments indicate that endogenous opioids, in particular β-endorphin, are released in purely rewarding situations. β-Endorphin may stimulate intake by supporting positive emotional reactions; in addition, it reduces negative reactions to aversive stimuli. This is consistent with the fact that β-endorphin produces positive emotional changes and that the aversiveness of antagonists, which reflects opioid blockade, is eliminated by destruction of the β-endorphin system in the brain. Such an emotional effect would also explain behavioural changes, for example, a decreased sensitivity to noxious stimulation and an increase in exploration tendencies. In nature, such changes might aid in foraging and in the formation of positive associations between environment and reward. Opioids lower the threshold for rewarding electrical stimulation to the brain. They also alter the response to sensory input and modify the initiation of motor activity. Naturally released opioids may, through effects on sensory processing, enable sensory input to excite more easily reward systems. Consistent with such a general effect are reports of opioid influences on several forms of motivated behaviour other than food and water intake. Some behaviours which are stimulated by aversive stimuli, such as shock-induced fighting and the need for closeness in social animals, are inhibited by opioids, whereas inter-male aggression is potentiated. Current results suggest that opioids suppress sexuality, perhaps through an interaction with hormones. Opioid effects on learning and memory can probably be explained in terms of their emotional actions.

Opioids and Motivation

Emotions, experienced subjectively, appear enigmatic and inaccessible to scientific analysis, but affect many concrete psychological phenomena, such as pain sensitivity and reactions to every-day experiences. Recent evidence suggests that opioid peptides, in particular β-endorphin, may influence motivational processes by affecting emotions. Opioid peptides are found in the nervous system and peripheral tissues and produce effects similar to those of opioid drugs. β-Endorphin, whose action has a long duration, may function as a hormone and as a neuromodulator, rather than as a classical neurotransmitter. It is released by stress and causes hyperthermia and an increase in threshold pain. Endogenous opioids also stimulate food and water intake. Biochemical and behavioural experiments indicate that endogenous opioids, in particular β-endorphin, are released in purely rewarding situations. β-Endorphin may stimulate intake by supporting positive emotional reactions; in addition, it reduces negative reactions to aversive stimuli. This is consistent with the fact that β-endorphin produces positive emotional changes and that the aversiveness of antagonists, which reflects opioid blockade, is eliminated by destruction of the β-endorphin system in the brain. Such an emotional effect would also explain behavioural changes, for example, a decreased sensitivity to noxious stimulation and an increase in exploration tendencies. In nature, such changes might aid in foraging and in the formation of positive associations between environment and reward. Opioids lower the threshold for rewarding electrical stimulation to the brain. They also alter the response to sensory input and modify the initiation of motor activity. Naturally released opioids may, through effects on sensory processing, enable sensory input to excite more easily reward systems. Consistent with such a general effect are reports of opioid influences on several forms of motivated behaviour other than food and water intake. Some behaviours which are stimulated by aversive stimuli, such as shock-induced fighting and the need for closeness in social animals, are inhibited by opioids, whereas inter-male aggression is potentiated. Current results suggest that opioids suppress sexuality, perhaps through an interaction with hormones. Opioid effects on learning and memory can probably be explained in terms of their emotional actions.

Effects of post-trial injection of β-endorphin on shock-induced fighting are dependent on baseline of fighting

The effects of repeated post-trial administration of 10 micrograms/kg beta-endorphin on the development of mutual fighting in pairs of rats submitted to various intensities of electric shock were investigated. beta-Endorphin blocked the development of fighting responses when a low footshock intensity was used, but facilitated it when a high shock intensity was delivered. A detailed analysis of the relationship between shock intensity, baseline of fighting, and effects of beta-endorphin showed that the effects of beta-endorphin were dependent on the behavioral baseline rather than on shock intensity per se.

Dose related effects of pentobarbital on the genetic differences seen between paired, Roman high- or low-avoidance rats in shuttle box

The effects of low doses of pentobarbital (PB) were measured on the activity levels, shock-induced fighting and avoidance or escape behavior of paired rats of two psychogenetically-selected lines, in multiple shuttle box sessions, following shock-induced fighting or two-way avoidance training. Each pair served as its own control, by receiving drug injections only every second week. Independent of training conditions, the RLA/Verh pairs showed about 90% freezing behavior and no fighting, whereas all RHA/Verh pairs preferred avoidance or escape behavior to fighting. Although their intertrial (shuttling) responses (ITRs) were reduced at the higher doses of PB used, RHA/Verh rats were still capable of most behavioral responses even at 24 mg/kg, whereas all RLA/Verh rats slept at that dose. On the other hand, the ITRs and avoidance responses of the (less active) RLA/Verh rats were increased by injections of 8 and 16 mg/kg PB. The results, especially those pertaining to freezing behavior and changes in activity levels, were discussed in comparison to other selected rat strains which have shown certain similarities to the Roman lines in regard to “emotionality” and associated neurochemical status.

Aggressive behavior inhibition by serotonin and quipazine injected into the amygdala in the rat

The effects on aggressive behavior, open-field activity, and pain threshold of bilateral microinjections of serotonin (20 micrograms) and quipazine (20 micrograms), the direct serotonergic receptor agonist, into the cortico-medial amygdala were investigated in Wistar rats. Both drugs significantly prolonged the attack latency in isolated killer rats (predatory aggression model), and suppressed the incidence of aggressive postures/attacks in shock-induced fighting test (affective aggression). The only difference in the open-field behavior was the lower number of central square entries in drug-treated compared to saline-injected rats. None of the substances produced any significant change in jump threshold. It is concluded that stimulation of serotonin receptors within the amygdala produces inhibition of affective and muricidal behavior in isolated rats. The effect does not seem to be dependent on changes in general activity and pain sensitivity.

Influence of shock-induced fighting and social factors on pituitary-adrenal activity, prolactin and catecholamine synthesizing enzymes in rats

The present experiment investigated changes in pituitary-adrenal activity, prolactin and catecholamine synthesizing enzymes in rats exposed to electric shocks in pairs or individually, in comparison to animals receiving no shock and tested in pairs or alone. Pairs of rats repeatedly exposed to electric shocks displayed a lower activation of the pituitary-adrenal system but a stronger activation of the sympathetic-adrenal medullary system than rats shocked individually. There was no differential release of prolactin according to the social setting in which shock occurred. Social factors by themselves influenced plasma corticosterone levels but not plasma levels of ACTH and prolactin nor catecholamine synthesis. These results are discussed in relation to the postulated beneficial effects of fighting on physiological activation produced by electric shock.

Regional changes in monoamines and metabolites following defensive aggression in the rat

Pharmacological studies have demonstrated that shock-induced defensive fighting is modulated by manipulations of the serotonergic, noradrenergic and dopaminergic neurotransmitter systems. In the present study, regional changes in 5-hydroxytryptamine, norepinephrine, dopamine and their metabolites 5-hydroxyindoleacetic acid, 3-methoxy-4-hydroxyphenylethylene glycol and 3,4-dihydroxyphenylacetic acid were measured following shock-induced fighting using high performance liquid chromatography coupled with electrochemical detection. Fighting produced reductions in the serotonergic, noradrenergic and dopaminergic systems and elevations in the noradrenergic and dopaminergic systems within the brain stem, hypothalamus, hippocampus, caudate and amygdala relative to shocked or non-shocked controls. These data demonstrate that the activities of these neurotransmitters are involved in defensive aggression in rats. The changes in catecholamines may indicate adaptive responses to stress, while the changes in serotonin may indicate a permissive function for serotonin depletion in defensive fighting.

Influence of shock-induced fighting and social factors on dopamine turnover in cortical and limbic areas in the rat

The present experiments investigated changes in dopaminergic mesocorticolimbic neurones originating from the A10 cell group, in animals exposed to electric shocks in pairs or individually, in comparison to animals receiving no shock and tested in pairs or alone. The social setting under which shock occured had no influence on the increases in DOPAC levels observed in animals exposed acutely or chronically to electric shocks. In contrast, subordinate rats in the paired shock condition had lower tyrosine hydroxylase activity in the accumbens than dominant rats. Pairing of animals in the test cage without shock induced an increase in accumbens DOPAC levels.

Effects of post-trial administration of naloxone and β-endorphin on shock-induced fighting in rats

To study the involvement of endogenous opioid peptides in the development of shock-induced fighting, naloxone (2 mg/kg) or beta-endorphin (10 micrograms/kg) was administered subcutaneously immediately after the session and during nine consecutive daily sessions to rats repeatedly exposed to electric shocks. beta-Endorphin blocked the development of shock-induced fighting while naloxone facilitated it but only when shock-induced fighting occurred at a low rate. The effects of beta-endorphin were time dependent since when beta-endorphin was injected 90 min after the shock session instead of immediately after, its impairing effect disappeared. In addition, naloxone blocked the impairment produced by beta-endorphin. Differential postsession treatment of each member of pairs of rats with naloxone and beta-endorphin resulted in a higher probability of rats treated with naloxone to be dominant over rats treated with beta-endorphin in the test situation. These results are discussed in relation with the possible involvement of endogenous opioids in the modulation of the physiological consequences of defensive behavioral responses to shock.

Behavioral studies in spontaneously hypertensive rats

In the present study we examined some behavioral patterns in spontaneously hypertensive (SHR) male rats as compared with Wistar (W) rats. The following methods were employed: open field test, two-way active avoidance, passive avoidance, shock-induced fighting, shock-induced suppression of drinking (conflict test), and dominant-subordinate behavior in rats competing for water. Spontaneously hypertensive rats showed higher level of locomotor activity, lower emotionality, lower anxiety level, increased acquisition of avoidance tasks, and enhanced dominance behavior. In addition, hypertensive rats were less aggressive in shock-induced fighting test. It is concluded, that spontaneously hypertensive rats seem to be hyperactive in terms of locomotor activity while their emotionality appears to be paradoxically reduced.

Increased shock-induced fighting with supersensitive β-adrenergic receptors

Adult male rats were treated chronically with haloperidol (1 mg/kg) daily or propranolol (10 mg/kg bid) and evaluated for changes in shock-induced fighting. Haloperidol suppressed fighting. Chronic propranolol facilitated fighting when rats were tested eight hours after injection. Acutely, either 5 or 10 mg/kg of d,1-propranolol suppressed shock-induced fighting. Chronic pindolol (10 mg/kg bid) and chronic 1-propranolol (5 mg/kg bid) administration increased fighting. Chronic d,1-propranolol, 1-propranolol or pindolol administration was associated with an increase in B max for β-adrenergic receptors. No change in fighting or B max was observed with the chronic administration of d-propranolol (5 mg/kg bid) or metoprolol (10 mg/kg bid). This increase in shock-induced fighting appears to be a behavioral response developing as a consequence of increased β-adrenergic receptors responding to endogenously released norepinephrine.