Brain serotonin metabolism in isolated aggressive mice

Giacalone, E.; Tansella, Michele; Valzelli, L.; Garattini, Silvio

doi:10.1016/0006-2952(68)90069-5

Cited by 112 publications

(34 citation statements)

References 45 publications

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“…A decrease in serotonergic activity in the nucleus accumbens has been associated with increased aggression (Giacalone et al, 1968;Haney et al, 1990;Welch and Welch, 1968) and impulsivity (Cardinal et al, 2001;Tobin and Logue, 1994). In contrast, an increase in serotonergic activity in the nucleus accumbens is associated with stressful conditions (Petty et al, 1994;Rueter and Jacobs, 1996;Wilkinson et al, 1996), such as in the forced swim test (Amat et al, 1998a;Amat et al, 1998b;Kirby et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

Corticotropin-releasing factor 1 and 2 receptors in the dorsal raphé differentially affect serotonin release in the nucleus accumbens

Lukkes

Forster

Renner

et al. 2008

European Journal of Pharmacology

100

129

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Corticotropin-releasing factor (CRF) is a neurohormone that mediates stress, anxiety, and affects serotonergic activity. Studies have shown that CRF has dose-dependent opposing effects on serotonergic activity. This effect has been hypothesized to be differentially mediated by CRF 1 and CRF 2 receptors in the dorsal raphé nucleus. We directly tested this hypothesis by using in vivo microdialysis to determine the effects of CRF and CRF antagonists in the dorsal raphé nucleus on serotonin (5-HT) release in the nucleus accumbens, a brain region implicated in the neuropathology of stress-related psychiatric disorders. Male urethane-anesthetized rats were implanted with a microdialysis probe into the nucleus accumbens, and CRF (0, 100 or 500 ng) was infused into the dorsal raphé. Infusion of CRF into the dorsal raphé nucleus had dose-dependent opposite effects, with 100 ng of CRF significantly decreasing 5-HT levels in the nucleus accumbens and 500 ng CRF significantly increasing accumbal 5-HT levels. In subsequent experiments, the raphé was pre-treated with the CRF 1 receptor antagonist antalarmin (0.25 µg) or the CRF 2 receptor antagonist antisauvigine-30 (ASV-30; 2 µg) prior to CRF infusion. Antagonism of CRF 1 receptors in the dorsal raphé nucleus abolished the decrease in accumbal 5-HT levels elicited by 100 ng CRF, and CRF 2 receptor antagonism in the raphé blocked the increase in accumbal 5-HT levels elicited by 500 ng CRF. These results suggest that the opposing effects of dorsal raphé CRF on 5-HT release in the nucleus accumbens are dependent on differential activation of CRF 1 and CRF 2 receptors in the dorsal raphé nucleus.

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Section: Discussionmentioning

confidence: 99%

Corticotropin-releasing factor 1 and 2 receptors in the dorsal raphé differentially affect serotonin release in the nucleus accumbens

Lukkes

Forster

Renner

et al. 2008

European Journal of Pharmacology

100

129

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“…Indices of low serotonin activity in the brain have been associated with increased levels of aggression and violent behavior, as measured by decreased 5-HT in brain tissue in aggressive mice (Giacalone et al, 1968;Welch and Welch, 1968;Haney et al, 1990) and by decreased levels of 5-HIAA in CSF in violent humans (Brown et al, 1982;Linnoila et al, 1983;Kruesi et al, 1990;Coccaro, 1992;Virkkunen et al, 1996;Kavoussi et al, 1997) and aggressive macaques (Higley et al, 1992(Higley et al, , 1996Mehlman et al, 1994). Selective serotonergic agonists at the 5-HT 1A and 5-HT 1B receptor subtypes, as well as serotonin reuptake inhibitors, have been proven very effective in reducing aggressive behavior in rodents and humans (Olivier and Mos, 1986;Olivier et al, 1987;Miczek et al, 1998;de Boer et al, 1999;Ferris et al, 1999;Fish et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

Aggressive Behavior, Increased Accumbal Dopamine, and Decreased Cortical Serotonin in Rats

2000

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Dopamine (DA) and serotonin have been implicated in the regulation of aggressive behavior, but it has remained challenging to assess the dynamic changes in these neurotransmitters while aggressive behavior is in progress. The objective of this study was to learn about ongoing monoamine activity in corticolimbic areas during aggressive confrontations in rats. Male Long-Evans rats were implanted with a microdialysis probe aimed at the nucleus accumbens (NAC) or medial prefrontal cortex (PFC); next, 10 min samples were collected before, during, and after a 10 min confrontation. Rats continued to display aggressive behavior while being sampled, and they performed two to six attack bites as well as 140 sec of aggressive acts and postures. Dopamine levels in NAC were significantly increased up to 60 min after the confrontation. Peak levels of 140% were achieved ϳ20-30 min after the confrontation. No concurrent changes in accumbal serotonin levels were seen during or after the confrontation. Dopamine and serotonin levels in PFC changed in the opposite direction, with a sustained decrease in serotonin to 80% of baseline levels during and after the confrontation and an increase in dopamine to 120% after the confrontation. The temporal pattern of monoamine changes, which followed rather than preceded the confrontation, points to a significant role of accumbal and cortical DA and 5-hydroxytryptamine in the consequences as opposed to the triggering of aggressive acts. The increase in accumbal DA in aggressive animals supports the hypothesis that this neural system is linked to the execution of biologically salient and demanding behavior. Key words: aggression; dopamine; serotonin; nucleus accumbens; prefrontal cortex; rats; microdialysis; behaviorThe proposal of a deficit in brain serotonin [5-hydroxytryptamine (5-HT)] as a trait marker for violence-prone individuals is based on measurements that are divorced from the actual behavioral event (Mann et al., 1995;Mann, 1999). In such individuals, low levels of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) were measured in CSF compared with nonviolent controls (Brown et al., 1982;Linnoila et al., 1983;Kruesi et al., 1990;Coccaro, 1992;Virkkunen et al., 1996;Kavoussi et al., 1997). In juvenile monkeys, low levels of 5-HIAA are correlated with increased risk-taking and impulsivity (Higley et al., 1992(Higley et al., , 1996Mehlman et al., 1994). If 5-HT undergoes dynamic state changes (Jacobs and Fornal, 1999) then in vivo measures would indicate whether altered serotonin actually is linked to the occurrence of episodes of aggression.In rodents, aggressive behavior is effectively reduced by treatment with 5-HT 1A and 5-HT 1B receptor agonists (Olivier and Mos, 1986;Olivier et al., 1987;De Almeida and Lucion, 1997;Simon et al., 1998;de Boer et al., 1999;Ferris et al., 1999;Fish et al., 1999). Furthermore, aggression is increased in 5-HT 1B receptor knock-out mice (Saudou et al., 1994). 5-HT modulates aggressive behavior in interaction with other neurotransmitters, of...

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“…The growing evidence that very short-lasting social stresses have profound, long-lasting effects upon physiological and behavioral functions strengthens the suggestion that social and population conditions have psychophysiological effects that importantly influence the maintenance of health and the development of [30][31][32]33 4 Since the tissues of our fighting mice were used either for chemical assay or for dry weight determinations, no histological studies have yet been made.…”

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confidence: 86%

Sustained Effects of Brief Daily Stress (Fighting) Upon Brain and Adrenal Catecholamines and Adrenal, Spleen, and Heart Weights of Mice

Welch¹,

Welch²

1969

Proc. Natl. Acad. Sci. U.S.A.

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Abstract.-Male white Swiss mice that had previously been made aggressive by several weeks of individual housing were allowed to fight for 5 to 10 minutes each day for 5, 10, or 14 consecutive days; fighting caused a marked enlargement of their adrenals, spleens, and hearts, and a large increase in adrenal catecholamines; brain catecholamines were slightlyincreased. Long-term group caging, under conditions where the mice did not fight, caused changes that were directionally the same but of smaller magnitude. Similar sociophysiological influences may be important in natural populations. Fighting mice, used under welldefined and closely controlled conditions, may be useful for studying normal mechanisms of neuroendocrine adaptation and control, and, possibly, for studying some forms of hypertension and cardiovascular-renal disease.Brief stressful experiences, either physical or emotional, may have profound long-lasting physiological effects.1-12 We have studied certain aspects of these effects by allowing male mice, previously made aggressive by long-term isolation, to fight for only 5 to 10 minutes on one occasion each day for 5, 10, or 14 consecutive days. These short daily periods of natural stress increased the weight of the adrenal, spleen, and heart, caused modest increases in catecholamine concentrations in the brain, and markedly increased catecholamines in the adrenal medulla.Methods. -Two fighting experiments were conducted using male white Swiss mice that were made aggressive by housing them individually for a number of weeks subsequent to weaning. They were kept in a quiet room containing no females and no other species of animal. In the first experiment, DUB/ICR mice (Dublin Laboratory Animals, Dublin, Va.) were housed either individually or in groups of eight for approximately 4 months, after which half of the isolated mice were placed together and allowed to fight for 10 min each day for 14 days. In the second experiment, "Specific Pathogen Free" CD-1 mice (Charles River Breeders, Wilmington, Mass.) were housed individually for approximately 2 months, after which they were either left undisturbed in their individual cages as controls or placed together and allowed to fight for only 5 min daily for either 5 or 10 consecutive days before sacrifice. The mice were housed in polyearbonate cages 7 X 11 X 5 inches in size. Their diet was unmodified Wayne Feed for Laboratory Mice. In order to avoid extraneous disturbances, the cages were not changed for any of the mice during the 5 to 14 day experimental periods. The mice fought in pairs in a cage strange to both mice, except that in the few instances when they failed to fight in pairs they were placed into groups of four in order to assure that they would be involved in fighting. The mice were randomly paired and, hence, were not with the same partner from one fighting period to the next. All mice were killed by decapitation 24 hr after the last fight. They were killed between 8:00 P.M. and 11:00 P.M., and a strict rotation was maintained between treatments...

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Brain serotonin metabolism in isolated aggressive mice

Cited by 112 publications

References 45 publications

Corticotropin-releasing factor 1 and 2 receptors in the dorsal raphé differentially affect serotonin release in the nucleus accumbens

Corticotropin-releasing factor 1 and 2 receptors in the dorsal raphé differentially affect serotonin release in the nucleus accumbens

Aggressive Behavior, Increased Accumbal Dopamine, and Decreased Cortical Serotonin in Rats

Sustained Effects of Brief Daily Stress (Fighting) Upon Brain and Adrenal Catecholamines and Adrenal, Spleen, and Heart Weights of Mice

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