PubMed Health⌕ Search

Biomedical subjects

B Siegfried

Publications and source records attributed to B Siegfried.

At least 19 recordsLinked to original sources
PubMed1993

Circadian activity, nociceptive thresholds, nigrostriatal and mesolimbic dopaminergic activity in the Naples High- and Low-Excitability rat lines.

These experiments were designed to further characterize the differential phenotypic constellation of the Naples High- (NHE) and Naples Low-Excitability (NLE) lines. In order to determine possible differences between NHE and NLE rats in activity and circadian rhythms, besides reactivity to novelty (selection trait), adult male rats of both strains were tested during two 10-min exposures to a Làt-maze. They were then kept in activity cages continuously for 3 days. Moreover, nociceptive thresholds were measured with the hot-plate and the tail-flick test, to probe the possibility that these rats could be differentially sensitive to nociceptive stimuli. Further, the integrity of the nigro-striatal and mesolimbic system was investigated by measuring tyrosine-hydroxylase activity in the striatum and 3,4-dihydroxyphenylacetic acid (DOPAC) levels in the striatum as well as in the nucleus accumbens. In addition, TH activity was measured in the adrenals to probe the sympathetic section of the neurovegetative system. The results indicate that NHE and NLE rats differ by a factor of two in their phasic activity in a Làt-maze. In contrast, no differences in 24-h activity during the dark or light phase could be observed in the activity cages. However, NHE rats anticipated the light-on stimulus in the morning by reducing their activity 1 h earlier than NLE rats. Further, no difference could be found with the hot-plate and the tail-flick test. Finally, biochemical analyses revealed no difference in the NHE and NLE rats in the main terminal zone of mesolimbic system (n. accumbens) nor of nigrostriatal system (striatum) nor in the adrenal glands. In conclusion, since the only consistent difference between NHE and NLE rats appears to be reactivity to spatial novelty, an hippocampus-dependent behavioral trait (selection trait), independent of altered activity in the sympathetic system or dopaminergic activity in the major dopaminergic brain systems, the usefulness of these strains as genetic model to test current hypotheses of spatial processor device(s) in the mammalian brain is supported.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1991

Strain-dependent effects of morphine injected into the periaqueductal gray area of mice.

1. Microinjection of morphine (0.31, 1.25 and 5.0 micrograms) into the periaqueductal grey area (PAG) of C57BL/6 (C57) and DBA/2 (DBA) mice increased the pain threshold in the tail-flick test. The highest dose also caused a behavioral reaction in both strains characterized by periods of immobility alternating with explosive motor behavior. 2. In the DBA strain, the analgesic effect was demonstrated with all doses of morphine, while in the C57 strain only the highest dose induced analgesia. 3. DBA mice presented a decrease in activity with the lowest dose of morphine, whereas in the C57 strain, this effect was obtained only with the highest dose of morphine. 4. These data corroborate at the PAG level the results of other studies which have shown that central and peripheral injections of morphine produce analgesia and alter motor activity in C57 and DBA strains. They also confirm that these two strains of mice present genotype-dependent differences in sensitivity to opioids as determined after injections of morphine into the PAG.

Animals↗
PubMed1990

An ethological model for the study of activation and interaction of pain, memory and defensive systems in the attacked mouse. Role of endogenous opioids.

The present work reviews neurochemical, physiological and behavioral data recorded from the attacked mouse and integrates them into a model of coping mechanisms during social conflict. More specifically, the possible relationships between systems of pain, memory and defense are presented, with special emphasis on the role of endogenous opioid peptides (EOPs). In recipients of attack, decreased beta-endorphin-like immunoreactivity and changes in opiate and benzodiazepine binding characteristics are found in structures of the brain defensive system. EOPs mediate the social conflict-induced increase of dopamine synthesis in the periaqueductal grey and frontal cortex. Social conflict analgesia in attacked mice is under the control of central opioid and nonopioid (e.g., benzodiazepine, glutamate) mechanisms, and is modified by experience (e.g., long-term analgesic reaction; tolerance). EOPs and pain-inhibitory mechanisms participate in the organization of behavioral defense, recuperative behavior and the memory of attack experience. The data are considered in relation to the perceptual-defensive-recuperative model of fear and pain, forwarded by Bolles and Fanselow.

Aggression↗
PubMed1990

[Not Available].

Explore the source record for details and available documents.

Germany↗
PubMed1989

NMDA receptor blockade in the periaqueductal grey prevents stress-induced analgesia in attacked mice.

Microinjections of N-methyl-D-aspartate (NMDA, 0.1 and 1.0 nmol) into the periaqueductal grey (PAG) of the mouse resulted in potential antinociception. In a social conflict situation, attacked mice exhibited a marked analgesia that was prevented by prior injection of the competitive NMDA antagonist, AP-7 (2.0 nmol) or naloxone (6.0 nmol) into the PAG and also by i.p. injection of the non-competitive NMDA antagonist, MK-801 (33 nmol). These results demonstrate that NMDA receptors are involved in endogenous analgesic mechanisms activated by stress.

Analgesia↗
PubMed1989

Relationship between behavioral and nociceptive changes in attacked mice: effects of opiate antagonists.

The relationship between analgesia and behavior during and after an aggressive encounter was investigated in saline- and opiate antagonist-treated DBA mice. A low number of bites induced an analgesia that was reversed by beta-chlornaltrexamine but not by naloxone, and that correlated positively with increased displays of defensive upright and immobility upon contact with the opponent. Extended attacks induced a naloxone-sensitive analgesia that was linked to a delayed occurrence of "panic" escape behavior. In the post-conflict phase, the degree of immobility and analgesia correlated positively in attacked mice. Naltrexone prevented this analgesia and lowered immobility. Endogenous opioids released during social conflict may induce analgesia and immobility in DBA mice.

Animals↗
PubMed1989

Beta-endorphin-like immunoreactivity levels in the hypothalamus, the periaqueductal grey and the pituitary of the DBA mouse: determination by ELISA and relationship to nociception.

The present paper describes the development and application of an enzyme-linked immunosorbent assay (ELISA) for the assessment of beta-endorphin-like immunoreactivity (beta-ELIR) level in the hypothalamus, the periaqueductal grey (PAG) and the pituitary of DBA/2 mice that were subjected to mild social stress (aggressive confrontation). After confrontation these subjects showed elevated tail-flick latencies (TFL) when compared to controls, a finding that indicates stress-induced analgesia (SIA). A positive correlation was found between individual TFLs and beta-ELIR levels in the PAG but not in the hypothalamus and the pituitary. These results suggest that individual baseline PAG beta-ELIR levels may be taken as a predictor of high degrees of stress-induced analgesia.

Agonistic Behavior↗
PubMed1989

Place avoidance learning and stress-induced analgesia in the attacked mouse: role of endogenous opioids.

In this study, mechanisms of pain inhibition (tail-flick test) and memory (place avoidance paradigm) were investigated in attacked, DBA/2 and C57BL/6, mice. During training, exposure of test animals to 10 or 30 bites by an aggressive, isolated ICR mouse situated in the dark half of a bright/dark conditioning box induced a significantly higher social conflict analgesia in DBA than in C57 mice. Naltrexone (0.5 and 2.0 mg/kg) reduced this response in DBA mice that received 30, but not 10, bites and was ineffective in C57 mice. This points to different, opioid versus naltrexone-insensitive nonopioid, analgesic mechanisms. During place choice testing in the same box 24 h later, DBA mice that had received 30, but not 10, bites showed a significant, naltrexone-reversible, avoidance of the attack place. No place avoidance learning was observed in C57 mice. The data provided unequivocal evidence that place avoidance learning was a result of associative conditioning, in that neither pairing nor social conflict per se significantly changed the preference for the dark side seen in experimentally naive DBA mice. Antagonism of place avoidance conditioning was observed regardless of whether testing was carried out in the drugged or undrugged state, excluding possible state-dependent effects as an explanation for the naltrexone-induced impairment. Individual correlational analysis in saline-injected, attacked DBA mice revealed a negative relationship between the analgesic state immediately after training and the avoidance of attack place during testing. In summary, the results suggest strain-dependent analgesic and learning mechanisms and indicate that endogenous opioids released in attacked DBA mice support pain inhibition and modulate the memorization of attack place by their analgesic effects, as well as by mechanisms independent of pain inhibitory systems.

Animals↗
PubMed1988

Recovery from opioid receptor alkylation: social conflict analgesia and brain [3H]etorphine binding in beta-chlornaltrexamine-treated mice.

The effects of beta-chlornaltrexamine (CNA, 5 mg/kg s.c.) on social conflict analgesia and brain opioid binding were investigated in mice at different times after the administration of the alkylating antagonist. The specific binding of [3H]etorphine to high-affinity binding sites and the stress-induced analgesia of attacked mice (50 bites) were prevented for 6 h after CNA administration. Stress-mediated inhibition of pain fully recovered within 3 days after CNA treatment. Brain opioid binding was still reduced to 45% at this time and reached control values 9 days after treatment.

Alkylation↗
PubMed1988

Opioids and behavior: genetic aspects.

Three animal models, based on genetic differences in endogenous opioid peptides and opioid receptors, are described. Obese mice and rats, whose pituitary opioid content is elevated, may be used to investigate eating disorders. Recombinant inbred strains of mice, which differ in brain opioid receptors and analgesic responsiveness, can be used for study of opioid- and nonopioid-mediated mechanisms of pain inhibition. Individual reactivity to opioids can be examined in C57BL/6 and DBA/2 inbred strains of mice. A model that combines a variety of opioid effects is offered and suggests the existence of a genetically determined dissociation of opioid effects on locomotor activity and pain inhibition. In addition, stimulatory locomotor responses in the C57BL/6 reaction type are linked to a high risk of drug addiction and facilitatory effects on adaptive processes, while high analgesic potency in the DBA/2 reaction type is accompanied by a low proneness to drug abuse and amnesic properties of opioids.

Animals↗
PubMed1988

Social conflict-induced changes in nociception and beta-endorphin-like immunoreactivity in pituitary and discrete brain areas of C57BL/6 and DBA/2 mice.

The present study characterizes the time course of social conflict analgesia and its reversibility by opioid antagonist drugs in the C57BL/6 and DBA/2 inbred strains of mice and examines the relationship between alterations in brain and pituitary levels of beta-endorphin-like immunoreactivity (beta-ELIR) and the antinociception elicited by social stress. Data revealed statistically significant strain differences in regard to beta-ELIR in control animals. The pituitary content of beta-ELIR was higher in DBA/2, while the values in the periaqueductal grey (PAG) and in the amygdala were higher in C57BL/6 mice. No interstrain differences were found in the hypothalamus. Exposure to 50 attack bites resulted in a 6-fold higher analgesia in DBA/2 mice and in a strain-independent fall of beta-ELIR in pituitary (approximately 27%) and PAG (23%). PAG but not pituitary beta-ELIR levels in C57BL/6 mice correlated positively with the increase in tail-flick latency after attack. Mere confrontation with a non-aggressive opponent failed to induce analgesia and was associated in C57BL/6 mice with a significant reduction in the beta-ELIR content of both the pituitary and the PAG. The data are discussed in terms of genotype-dependent sensitivity of the beta-endorphin system to stress and its relation to analgesia.

Aggression↗
PubMed1988

Emergence and development of stress-induced analgesia and concomitant behavioral changes in mice exposed to social conflict.

Mice of the inbred strain DBA/2, when exposed to a social conflict, developed a low intensity, naloxone-insensitive analgesia after 15 bites, and a more pronounced naloxone-sensitive analgesia after 45 bites. The effective inhibition of the antinociceptive response following low and high number of bites by the alkylating opiate antagonist beta-chlornaltrexamine suggests participation of opioid mechanisms at both stress levels. Emergence of an increased tail-flick latency was indicated by the occurrence of defensive upright postures upon contact with the opponent, while animals displaying full analgesic response during the period of bite 31-45 increased their escape reactions without being in contact with the aggressor. Suppression of social conflict analgesia in mice by pretreatment with opiate antagonists facilitated the occurrence of these escape reactions. The display of panic escape responses is discussed in the context of increased fear and helplessness that developed under conditions of sustained attacks.

Aggression↗
PubMed1988

Isolation-induced locomotor hyperactivity and hypoalgesia in rats are prevented by handling and reversed by resocialization.

Differences in locomotor activity in the open field were found between individually and group-housed rats (isol greater than soc). Daily handling, initiated at postnatal day 1, was without effect in group-housed rats but prevented the isolation-induced hyperactivity. For tail-flick latency, strikingly similar differences (isol greater than soc; prevention by handling) have been observed. The isolation-induced aberrations in both locomotor reactivity in a novel environment and in pain sensitivity could be reversed by subsequent resocialization. This indicates that the altered sensitivities to external stimuli are caused by the environmental manipulation.

Animals↗
PubMed1988

Naltrexone-reversible pain suppression in the isolated attacking mouse.

Fighting pairs of isolated DBA/2 mice showed a significant increase in tail-flick response latencies independent of whether opponents were losing or winning the combat. The effect lasted less than 10 min in both animals. Elevated pain thresholds were also found in isolates that attacked a nonaggressive conspecific, and were prevented by naltrexone (0.2 mg/kg), while a larger dose (1.0 mg/kg) inhibited the attack behavior. A small increase in pain threshold was observed after exposure of isolates to the test box alone, while isolation per se had no effect on baseline tail-flick latencies. The data demonstrate that endogenous pain suppressing systems are activated during attack and suggest that this opioid-mediated antinociception is a correlate of the isolation syndrome, reflecting enhanced arousal of the attacking animal.

Aggression↗
PubMed1988

Construction and reconstruction of memories.

1. Recent evidence suggests that treatments given after training may influence memory in two ways: by becoming themselves incorporated to the experience, or by altering post-training mechanisms involved in the storage of the experience. The two processes may be called consolidation. 2. Some endogenous substances that are normally released during or after training (brain beta-endorphin; the peripheral stress hormones, ACTH, epinephrine and vasopressin) appear to be of particular importance. Their effect may become incorporated to the experiences as a conditioned stimulus (CS), generating state dependency. The effect of beta-endorphin appears to be physiological, since the substance is released by novel experiences. 3. Post-event information provided by other training experiences, in rats, or by comments or leading words, in humans, may also incorporate to the experiences, altering their content qualitatively or quantitatively. 4. A variety of substances including the stress hormones at low doses and analeptic drugs may facilitate retention when given after training. In this case, the effect is best explained by an enhancement of the post-training strengthening of memory traces. 5. The reiteration of part of the experiences at the time of testing facilitates retrieval. This may be viewed as a reconstruction of consolidation at the time of retrieval, and may be obtained using cognitive material ("priming"), or neurohumoral stimuli (a beta-endorphin injection, or a presumable release of brain beta-endorphin by an interpolated novel experience). The effect can be seen in animals rendered amnestic by electroconvulsive shock, and in humans with amnesia of organic and non-organic nature. 6. The human amnesic syndrome seems, thus, largely explainable by a deficit of retrieval. It is possible that the stimulation of retrieval by priming, or by drugs, through the "reconstruction" of consolidation, may be useful for the relief or treatment of the human amnesic syndrome.

Amnesia, Retrograde↗
PubMed1987

Effects of repeated as compared to single aggressive confrontation on nociception and defense behavior in C57BL/6 and DBA/2 mice.

Behavioral reactions (submissive postures, escape, immobility, activity, locomotion) in C57BL/6 and DBA/2 test mice were recorded during single (50 bites) or three repeated (3 X 50 bites, separated by 24 hr) aggressive confrontations, as well as during a nonaggressive confrontation 24 hr after the last aggressive confrontation with opponents of the opposite strain. Nociception (hot plate response latency) was measured 1 min after aggressive or nonaggressive confrontations. During repeated aggressive confrontation, DBA mice reacted with a stable pattern of escape and analgesia, whereas C57 mice failed to develop an analgesic response and changed their behavioral defense strategy during repeated aggressive confrontations (decrease of escape, increase of defensive upright). The conditioned display of submission and of escape behavior during nonaggressive confrontation did not change as a function of earlier repeated aggressive confrontations in DBA mice, while C57 mice showed a significant increase of defensive upright postures and immobility. Conditioned analgesia was not observed after nonaggressive confrontations. The results point toward a dissociation between attack-elicited behavior and antinociception and suggest that encounter-induced analgesia may influence the processing of aversive experience.

Aggression↗